Longevity

Things That Decline with Age

Bones and Skeletal System:

In men, bone density diminishes at age 35. In women, peak bone density is age 30, and postmenopausal women experience an accelerated rate of bone loss. Foot arches become less pronounced, contributing to reduced height. The discs that separate the vertebrae lose fluid, the long bones become brittle due to mineral loss, joints become stiffer and less flexible and can lose some of their fluid, causing cartilage to rub together and wear out. Calcification in and around the joints also occurs. After 30, skeletal muscle mass declines more than 20% in both men and women in the absence of exercise, muscle loading, adequate protein, and heat stress. Strength and flexibility decrease, along with coordination, balance, and height. The CNS has a reduced ability to recruit muscle fibers, posture deteriorates and the risk of breaking bones increases. The gradual breakdown of joints leads to inflammation, joint pain, stiffness, and even physical deformities.

• Physical activity – particularly stressing the muscle and long bones of the skeletal systems – can help to slow many of these mechanisms down, as can regular sauna exposure, healthy protein intake, and PEMF therapy.

Digestive System:

Digestive activity decreases, leading to constipation, which may be exacerbated by medications like proton pump inhibitors and antibiotics, and by medical conditions, such as diabetes, and IBS. Peristalsis slows down, causing waste to move more slowly through the colon, leading to more water loss, exacerbating constipation further.

Diverticulosis can develop when small pouches in the lining of the colon bulge through weak spots in the intestinal wall. This can lead to gas, bloating, cramps, and even more constipation. If the pouches get inflamed, abdominal pain, cramping, fever, chills, nausea, and vomiting can occur. Cancerous or non-cancerous polyps can also form.

Gastroesophageal reflux disease (GERD) occurs when stomach acid rises into the esophagus, causing heartburn and other symptoms. Natural digestive enzymes decrease with age, leading to a loss of protein absorption, further aggravating sarcopenia. Research has shown that people with chronic diseases or poor energy levels tend to have fewer enzymes in their blood, urine, and tissues.

• Chewing food more thoroughly, eating adequate fiber and fermented foods, supplementing with digestive enzymes, and consuming amino acids, along with gut health strategies, can all slow the aging of the digestive system and depletion of enzymes.

Respiratory System:

Maximum lung capacity and maximum oxygen utilization (VO2 max) decrease gradually after about age 25, especially if you’re not frequently exercising. You also experience a drop in vital capacity, a weakening of respiratory muscles, and a decline in the effectiveness of lung defense mechanisms, including reduced WBCs on the surface of the lung alveoli.

As the diaphragm and other muscles weaken, you experience a decreased ability to breathe enough air in and out, as well as a decreased ability to keep airways open. Alveoli lose shape and become less functional.

• Regular cardiovascular exercise and breathwork practices can help to support the aging respiratory system. After all, lung volume is the greatest predictor of health and longevity.

Urinary System:

After age 30-40, 2/3 of us undergo a gradual decline in the rate at which our kidneys filter blood. The kidneys begin to lose tissue, and the number of filtering units known as nephrons decreases. The blood vessels that supply the kidneys can harden, further impairing the kidney’s filtration rate.

The bladder wall loses elasticity, meaning it cannot hold as much urine, and the muscles controlling the bladder weaken. The urethra can become blocked by an enlarged prostate gland in men or by a prolapsed bladder or vagina in women. Medical conditions, like diabetes, can contribute to incontinence.

• Deep pelvic core training, adequate hydration and mineral intake, limited consumption of dehydrating foods, such as alcohol and caffeine, and avoidance of excess protein.

Reproductive System:

For women the menstrual cycle stops at around 51 and the ovaries halt production of estrogen and progesterone. The ovaries stop producing eggs, and after menopause, you can no longer become pregnant. Vaginal walls become thinner, drier, less elastic, and possibly irritated. Vaginal yeast infection risk increases, and the external genital tissue and breast tissue thins. The pubic muscle can lose tone, resulting in prolapsed vagina, uterus, or bladder.

Testicular tissue mass decreases and testosterone gradually declines, along with blood flow to the reproductive organs. The volume of fluid remains consistent, with fewer sperm.

• Maintain regular sexual activity with age.

Endocrine System:

At 30 years old, HGH begins its regression in both men and women and declines at a rate of around 14% per decade. When women transition into menopause, progesterone, testosterone, and estrogen levels begin to fall. At 50, thyroid activity beings to decrease, and hyper or hypothyroidism may occur.

At 50, men may begin to experience andropause. In both men and women, a decline in DHEA can cause increased vulnerability to a variety of cancers.

At 60, as insulin production decreases and insulin cell receptor sensitivity lowers, the ability to metabolize sugar declines, and insulin resistance or diabetes becomes more prevalent.

At 70, hormones that protect against loss of calcium in bones decline, making osteoporosis more prevalent.

• Organ meat consumption, regular sex, care for the gut, and avoidance of modern plastics and endocrine-disrupting chemicals.

Circulatory System:

At around 40, your heart muscles thicken and blood vessels stiffen, causing the heart to fill more slowly (this can occur earlier if you’re a hard-charging athlete). Increasing blood pressure as the heart works harder, and possibly cardiac arrhythmias. The receptors that monitor blood pressure can also deteriorate, causing dizziness when you stand up from sitting or lying down. Further exacerbated by calcification or excess calcium deposits in the body, manifesting as stiffening of joints, plaque buildup on the teeth, hardening of the arteries, impaired brain function, and general aches and pains.

Many individuals over 60 have enlarged deposits of calcium mineral in their arteries, often caused by a lack of minerals in their diet, dehydration, limescale in tap water, and even synthetic calcium supplements.

Abnormal heart rhythms can develop, leading to arrhythmias like atrial fibrillation. The pacemaker can develop fibrous tissue and fat deposits in some of its pathways and lose some of its cells, resulting in a slower heart rate. The walls of capillaries can thicken, resulting in a slower rate of exchange of nutrients and waste products.

The total water content of blood falls, RBC production falls, and certain WBCs deteriorate. Lymph fluid can stagnate, toxins accumulate, and immune cells are not delivered to the areas of the body where they are most needed. Weakening the immunity and infection fighting ability.

• Regular cardiovascular exercise, hydration, regular exposure to heat and cold, and the lymph-fluid-circulating strategies.

Nervous System:

Some nerve structure and function are lost. Waste products can collect in brain tissue, causing plaques and tangles. Alzheimer’s and other forms of dementia then increase in risk. Plaques are actually a part of the immune system and release antimicrobial agents to deal with bacteria, viral, or fungal infections in the brain.

By age 40, the lenses in the eyes begin to stiffen, resulting in vision impairment, particularly when focusing on near objects. Hearing loss may develop, which occurs in men sooner than women, and memory tends to worsen.

Skin:

Stem cell production and availability both decline with age, and a result of this is that the skin’s epidermal cells slow in their reproduction. Melanocytes, which produce pigmentation, decrease in number while the remaining cells increase in size. This can cause thinner, more translucent skin, as well as large pigmented spots. Skin injuries, tearing, and infections become more frequent.

Loss of fat and collagen in the underlying tissues can cause skin to sag and wrinkle, and the connective tissue loses its strength and elasticity. The blood vessels become more fragile, and bruising and bleeding under the skin, cherry angiomas, and other conditions become more frequent.

The skin becomes dry and itchy as the glands that produce oil reduce their production levels. The fat layer beneath the cutaneous layer of skin thins, leading to increased risk of skin injury and a reduced ability to maintain a consistent body temperature. Sweat glands produce less sweat, making it harder to cool off.

• Stem cell-supporting strategies, along with beauty tactics can help to minimize effects.

Underlying Causes

Chronic Inflammation

• Alzheimer’s
• Stroke
• Chronic lower respiratory disease (asthma)
• Cancer
• Diabetes
• Heart disease
• Influenza and pneumonia

Glycation

Glycation occurs when sugars in the bloodstream attach to proteins to form harmful molecules called advanced glycation end products. The more chronically elevated your blood sugar levels, the more likely it is that AGEs will develop, which can cause inflammation and cell membrane damage that can result in the development of diabetes, atherosclerosis, chronic kidney disease, and Alzheimer’s.

Track hs-CRP levels, get an inflammatory panel (myeloperoxidase, Lp-PLA2, dimethylarginine, oxidized LDL, prostaglandins, and fibrinogen), and glycemic variability tests like blood glucose and hbA1c. A Dexcom G6 can give better continuous glucose monitor data.

Methylation Deficits

The process of transferring a methyl group from one molecule to another, a crucial biological process involved in removing toxins, growing and repairing cells, and metabolic functioning. Methylation deficits are linked to a number of health conditions, including diabetes and cancer, and are caused by a variety of factors, including stress, nutrient deficiencies, and genetics.

A methyl group is a carbon atom attached to three hydrogen atoms. It is an abundant organic compound derived from methane. Methylation occurs when a methyl group is taken from one compound or molecule and is transferred to another. For example, a methyl group can be added to your DNA from a methyl donor like methionine (high amounts in meat tissue). The process is largely responsible for switching genes on and off and silencing viruses. When your body experiences methylation, less desirable genes, such as those that code for cancers and autoimmune diseases are switched off while helpful genes are switched on. Methylation is required for cell division, neurotransmitter synthesis and metabolism, detoxification, cellular energy metabolism, the formation of protective myelin sheaths, and early CNS development.

Undermethylation occurs when your body is unable to adequately transfer methyl groups or because you are not consuming enough methyl donating foods. This can cause you to be dopamine-seeking, hard-charging, high achiever, as it can keep serotonin levels low. It is associated with being an over-achiever, having OCD tendencies, a low threshold for pain, and ritualistic behaviors. Eat more meat and less folate (it acts as a serotonin reuptake inhibitor). SSRIs may be received well.

Over-methylation is associated with creativity and sensitivity. If you are prone, you may exhibit high levels of empathy for others but also experience sleep issues, food and chemical sensitivities, hyperactivity, panic attacks, and a tendency to gain unwanted weight. Highly correlated with schizophrenia. Eat less meat (vegetarianism and veganism may be beneficial). You need to consume adequate protein but don’t go overboard with muscle meat.

Degrading Mitochondria

A number of cell biologists have proposed the number and functionality of mitochondria can determine your potential for longevity. The free-radical theory posits that the oxidation of cells by ROS plays a leading role in the weakening of vital functions in aging organisms. Since mitochondria exhibit less damage in women than men, it is assumed this is why they tend to live longer. Poor lifestyle factors, such as bad air, unclean water, artificial light, electrical pollution, inflammation, a nutrient-poor diet low in antioxidants, lack of exercise, and many other factors can contribute to poor mitochondrial status. Mitochondrial DNA has limited ability to repair itself and is therefore more likely to undergo mutation than human DNA. Mitochondria usually gets damaged during periods of chronic inflammation and increased ROS, resulting in inefficient energy production and production of more free radicals.

Fatty Acid Imbalances

A diet high in omega-6 and low in omega-3, DHA, and monosaturated fats can create deficits or imbalances in fatty acids.

Immune Dysfunction

Autoimmune diseases develop when your immune system turns on itself, resulting in inflammation and organ and cell damage. Rheumatoid arthritis, lupus, MS, thyroid disease, and inflammatory bowel disease are becoming more common in the era of chemical exposure, antibiotic overuse, and unhealthy guts.

Telomere Shortening

Telomeres prevent chromosomes from becoming damaged or tangled with one another. When damaged, they can cause the destruction of genetic information, leading to cellular malfunction, which increases your risk of disease and overall mortality. Telomerase is an enzyme that lengthens telomeres and keeps them from wearing out too fast or too early and can be affected by lack of exercise, chronic stress, low plant consumption, and a lack of mindfulness practices such as meditation and yoga.

The number of times a cell can replicate before it is no longer protected by telomeres and dies is called the Hayflick limit. Shortened telomeres are linked to a weakened immune system and chronic and degenerative diseases like heart diseases and heart failure, diabetes, cancer, and osteoporosis.

Perceived levels of stress are correlated with telomere length. Feeling like you feel more stress leads to shorter length.

By middle age, telomeres are much longer in people that exercise. Which appears to be contributed to by reduced perceived stress levels and inflammation.

• Epitalon (synthetic peptide) is modelled after epithalamin, which is produced by the pineal gland. It appears to turn on apoptosis and slow tumor growth.
• TA-65 (cycloastragenol) also activates telomerase. It is a concentrated extract of astralagus.

DNA Expression

Nutrient depletion and other environmental factors, such as electrical pollution and poor air, light, and water, can alter gene expression. Conscious thoughts and emotions can also affect our genes.

Shrinking Tissues

As you age, stem cell reserves deplete and age, becoming less efficient. As well as mitochondria not triggering apoptosis at the right times. Keeping mitochondria healthy can reduce unnecessary cell loss.

Zombie Cells

Death-resistant cells, aka senescent cells, are cells that won’t die when worn out. They won’t divide or function properly either. Releasing inflammatory proteins, causing chronic inflammation. Mitochondria in these cells become dysfunctional and release huge amounts of ROS (senescence associated mitochondrial dysfunction).

Zombie cells are a precursor to type 2 diabetes, increased visceral fat, and symptoms of aging like arthritis.

Keep cell membranes strong by consuming calcium, magnesium, and potassium salts of amino ethanol phosphate. Metformin is believed to kill senescent cells. Rapamycin inhibits a growth pathway called mammalian target of rapamycin (mTOR), which is responsible for regulating cell growth, cell death, proliferation, and autophagy. Inhibiting mTOR appears to prevent senescent cell growth. Fisetin is a polyphenol found in seaweed and strawberries that has been shown to kill up to 50% of senescent cells in a particular organ. Ashitaba has been used for high blood pressure, hay fever, gout, and digestive issues, but it also contains dimethoxychalcone, which slows cell senescence. Piperlongumine (PPL), used in Ayurvedic medicine. PPL may have cancer fighting benefits but needs more research and may load the liver too much (suggests taking glutathione to support the liver).

Cellular Straightjackets

Extracellular matrix stiffening results in the body needing to work harder to pump blood. When sugar in your blood permanently binds with proteins, creating inflammatory advanced glycation end products (AGEs). The most abundant AGE in collagen is glucosepane, which contributes to diseases of aging like diabetes and vascular dysfunction.

Chronic inflammation is also associated with an increase in cross-linked proteins. 

Extracellular Junk

When waste products like amyloids start to accumulate, they stick together and form plaques, getting in the way of normal cellular function. Alzheimer’s is associated with beta-amyloid and type 2 diabetes is associated with islet amyloid inhibiting insulin secretion. Protein aggregates also cause a stiffening of the heart (senile cardiac amyloidosis).

Autoimmunity makes protein aggregation worse and so does low insulin levels in the brain (brain amyloid formation specifically). Reduce foods you are sensitive to and calm down to reduce inflammation and chronic stress. Vitamin D apparently helps to prevent protein malformation and sticking together.

Excess copper can be toxic and bind proteins, preventing clearance. Lead, arsenic, mercury, nickel, uranium, and cadmium exposure can impair mitochondrial energy production and cell death. Conflicting information to Morley Robbins’ “Root Cause Protocol”.

Junk Buildup Inside Cells

Lysosomes incinerate unwanted materials. When they can’t break products down, they sit there clogging up a cell until it can no longer function (intracellular aggregation). This results in loss of cells and tissue atrophy. This can happen if lysosomes are damaged, if they don’t have enough of the 60 types of enzymes required, or when exposed to excess ROS from dysfunctional mitochondria. AGEs can get stuck inside your cells, making cells more dysfunctional. Fried and charred foods contribute to these AGE levels.

Habits to Enhance Longevity

1. Don’t Smoke:

In childhood, telomeres are about 15000 base pairs long, but by old age they have shortened to about 3000. The oxidative damage from smoking a pack a day destroys an additional 5 each year. So, if you smoke for 40 years, that’s an extra 7 years cut off your life. Secondhand smoke contributes to severe asthma attacks, respiratory infections, ear infections, SIDs, coronary cancer, etc.

Downsides of smoking:

• Habit formation from the effects of nicotine of the CNS
• Withdrawal symptoms like anxiety, irritability, depression, headaches, and sleep problems when you try to quit
• Emphysema
• Chronic bronchitis
• Lung cancer
• The constriction and damage of blood vessels, which can lead to peripheral artery disease
• Hypertension
• Increased risk of stroke

You can support your adrenals by taking St John’s wort or ginseng, minimize damage to arteries with taurine (once a day for 2 months), a diet rich in proanthocyanins to regenerate skin and collagen (red wine, grapes, apples, blueberries, blackcurrants, hazelnuts, pecans, and pistachios), and polyphenols to repair lungs, alveoli, and bronchioles (kale and sprouts). Four cups of green tea per day helped the smokers’ stem cells (43% increase) and blood vessels (29% increase in function) to recover.

Six hours after quitting, circulating levels of carbon monoxide will decline, and your heart won’t have to work so hard to pump oxygen. 12 weeks in, your lung function will significantly improve and coughing, sinus congestion, shortness of breath, and fatigue levels will decline. Cilia regrow. 3 months in, your sexual performance will improve as testosterone levels will normalize. 9 months, your risk of cardiovascular complications will fall. After 1 year, it will be like you never smoked.

Strategies to reverse the damage of smoking:

• Foods high in vitamin E, like eggs, nuts, and dark leafy greens
• Foods high in CoQ10, like salmon, beef, broccoli, and avocado
• Vitamin C-rich foods that contain high amounts of bioflavonoids, like grapefruit, spinach, and citrus fruits (especially kiwi)
• Foods rich in vitamin B complex, like dark leafy greens, eggs, fish, and liver
• A full spectrum multivitamin rich in antioxidants

2. Eat Plants:

Plants deliver plenty of fiber, including insoluble fiber, a natural anticancer agent, antioxidants, oxidized cholesterol reducers, blood-clotting factors, and essential minerals. Wild plants possess a natural built-in defense that causes a hormetic response that can allow the body to better mount its own antioxidant defenses. Trace amounts of saponins in quinoa; lectins in soy and potatoes; gluten in rye, wheat, and barley; anthocyanins in berries; resveratrol in grape skins and red wine; EGCG in green tea; sulforaphane in broccoli and other cruciferous vegetables; catechins in cacao; and other controversial compounds can actually be good for you. Eating on the Wild Side by Jo Robinson, advises tearing up plants like kale hours before eating them to allow the chemical defenses to be released which apply mild stress on your body.

Muscle meat is high in methionine and low in glycine (mortality risk factor). Consume the offal for glycine.

If eating a plant restricted diet, build cellular resilience by sauna visits, cold thermogenesis, fasting, exercise, and exposure to sunlight. If you have gut issues, like IBD, diverticulosis, or diverticulitis, you may want to be careful about excessive fiber intake from plant matter and should choose herbs and spices over big salads and kale smoothies.

3. Avoid Processed and Packaged Foods:

Refined carbohydrates, artificial flavors, processed vegetable oils, and natural sweeteners are very rare in longevity hot spots (Blue Zones). Their versions of guilty pleasures are antioxidant-rich treats like red wine, sake, coffee, herbal tea, or simple desserts such as nuts, cheese, and berries or grapes. Nutritional evaluations have revealed Blue Zones tend to have a high consumption of whole, real foods that your great-grandparents would have recognized and a nutritional profile similar to the Mediterranean diet. They included plenty of herbs such as thyme and rosemary, low-GI carbohydrates that are free from sugar, healthier starches such as purple potatoes, yams, taro, or lentils, and foods high in natural fats such as extra-virgin olive oil and fish.

Ancestral diets:

• A predominantly Northern European ancestry may eat plenty of fermented foods, meats, fish, berries, and raw dairy, without large intakes of citrus fruits or other foods not likely encountered. Scandinavian ancestors would have access to fish rich in omega-3s and vitamin D.
• MTHFR mutations that create a poor ability to methylate tend to cluster in regions and populations where a group’s diet was rich in folate. Mexicans, Hispanics, Italians, and Chinese were more likely than others to carry MTHFR mutations that increased a need for dietary folate (leafy greens, organ meats, and pastured egg yolks).
• The AMY1 gene, which codes for salivary amylase production and helps break down starch and carbohydrates, helps to produce more amylase in those that tended to have a higher starch diet. Meaning you may be able to handle slightly higher amounts of carbohydrates. Japanese, continental Europeans, or populations that are high-starch foragers, such as the Hadza tribe in Tanzania, have been shown to possess more AMY1 copies than populations that consume less starch (sweet potato, yam, plantain, other roots and tubers, fruit, and rice), such as those areas of Turkey and the Congo.
• The lactase persistence gene enables an adult to digest lactose, without getting gut distress and diarrhea. Cultures that have not traditionally raised livestock, including those of Asia, Africa, and most of India, rarely carry the lactase persistent gene. If you are of European descent, you are probably lactose tolerant.

4. Eat Legumes:

A dry fruit contained within the shell or pod of a plant (beans, peas, peanuts, and alfalfa). Beans seem to reign supreme in the Blue Zones. Black beans (Nicoya), lentils, garbanzo beans, and white beans (Mediterranean), soybeans (Okinawa). Legumes are rich in plant protein, vitamins, minerals, appetite-satiating and gut-supporting fiber, along with slow burning carbohydrates. They require sprouting, fermenting, and soaking to make them bioavailable.

5. Incorporate Low-Level Physical Activity Throughout the Day:

Gardening, walking, farming, time in nature, chores with their hands, and spurts of high-intensity movement such as yoga, tai chi or qigong, hiking, and games or social sports.

Unless you are a professional athlete, there is no need to train like one.

6. Prioritize Social Engagement:

In Blue Zones, strong relationships are tied into the culture. They are more engaged and conscientious towards one another, more helpful and willing to empathize and express emotions. Eating, cooking, dancing, celebrating, helping to raise children, general support, etc.

7. Drink Low-to-Moderate Amounts of Alcohol, Especially Wine

Polyphenols and social interaction. Personally, I wouldn’t advise this step, but moderation, blah, blah, blah. People get upset when you take away their drugs. 

8. Restrict Calories and Fast:

• Time-restricted feeding: consuming all food within a three-to-twelve-hour window each day, so you fast for at least twelve hours daily
• Alternate-day fasting: fasting for twenty-four hours, then eating normally, then fasting for twenty-four hours again, and so on
• Eat-stop-eat: fasting for twenty-four hours once or twice a week
• Fasting-mimicking diet: consuming small amounts of food, about 40 percent of your usual calories, for three to five consecutive days
• Feast-famine cycling: eating according to the seasonal availability of foods
• Warrior diet: fasting during the day and eating a huge meal at night

9. Possess a Strong Life Purpose:

Ikigai (reason for being – Japan) or plan de vide (reason to live – Nicoyan)

10. Have Low Amounts of Stress:

Ruthlessly eliminate haste and hurry from your life. Breathwork is one of the best stress-reducing methods. A slow respiration and a high tolerance for CO2 seems to correlate with longevity in animals.

11. Engage in a Spiritual Discipline or Religion, or Believe in a Higher Power:

Churchgoers were 46% less likely to die in the follow-up period after a study compared to non-churchgoers. Many religious communities in the Blue Zones (seems to me to be more about community and safety than actual benefits from religion). 

12. Remain Reproductively Useful:

Don’t retire, don’t stop learning, be a valuable member of society, continue to have sex, have children or both. The Reproductive Potential Hypothesis, which maintains that life-span regulation has evolved in such a way as to maximize individual reproductive success, and research has shown that women who bear children later or bear more children experience enhanced longevity. Aging exists because natural selection is weak and ineffective at maintaining survival, reproduction, and cellular repair as we enter old age.

Dr. Michael Rose (Does Aging Stop): Have children early and continue to have them as late as possible, or at least keep having sex.

Advanced Antiaging Biohacks and Strategies

1. Longer-Term Fasting

Feast-Famine Cycling:

• Weston Price: Native Americans cycled between the summer cultivation of starches and fruits and far greater reliance on fats from animals (particularly organ meats and marrow) during winter. 9 months of the year was limited to wild game, such as caribou and moose. During the summer, they were able to use growing plants. During the winter some use was made of bark and buds of trees.
• Use fat instead of glucose during the winter months. Giving the digestive system a rest and cells a chance to engage in natural cell turnover.
• Dr. Pompa’s 5-1-1 strategy: Seasonal eating with cyclic ketosis. For 5 days, follow a low-carb, ketogenic diet, or especially if you’re trying to lose weight, a calorie-restricted diet (primarily local and seasonal foods). 1 day of the week, fast for 24 hours. The remaining day of the week, have a feast day, eating any of your favorite healthy foods, especially carbohydrates, until you’re full. You could also do a 4-2-1 or a 2-2-3 as a better fat-burning approach. Bonus points if you eat seasonally, such as more carbohydrates in the warmer months and more proteins and fats in the colder months: fresh fruit and berries in the spring, tubers and squash in the fall, heavier cuts of meat and fermented foods in the winter.

Fasting-Mimicking Diet:

• Valter Longo (The Longevity Diet): Alternate-day modified fasting, which is eating minimal calories every other day for a 24-hour period. Or an extended FMD, which is the program Longo advocates, which involves consuming minimal calories for 5 consecutive days.
• Completely fast for 24 hours, then eat to satiety for the following 24 hours. Better than caloric restriction at maintaining long-term weight loss and allows autophagy. 3–5-day fasts can stimulate autophagy, weight loss, and long-term reduction of IGF-1, glucose, and markers of inflammation and aging.
• Low in calories and protein. Meals are 360 calories each: 9% protein, 44% fat, and 47% carbohydrates. The diet is followed for 5 consecutive days with 3 meals on the first day (1090 calories), and 2 meals on each of the next 4 days (725 calories each day).

2. Hormetic Stress

Lift heavy stuff, don’t take or eat foods full of antibiotics, engage in hot-cold contrast therapy, eat plants with a high polyphenol content, drink wine for its polyphenols and similar compounds, such as tannins and anthocyanins, etc.

Hyperbaric Oxygen Therapy (HBOT):

• 100% oxygen, typically via a full-body chamber or a face mask. Often used to treat decompression sickness, infections, air bubbles in your blood, and wounds that are not healing well. High pressures to enhance oxygen delivery to tissues.
• Oxygen binds to hemoglobin in your RBCs. HBOT results in a 20-fold increase in blood plasma oxygen levels, including a significant increase in RBCs. It promotes tissue repair, the formation of new blood vessels, wound healing, and the controlled release of ROS in damaged and infected tissues, which can stimulate a beneficial hormetic response. HBOT may have an antifungal effect, caused by the reversal of fungal growth and restoration of a normal immune system. Treatment may induce mitochondrial biogenesis and DNA repair.
• After a concussion, 60-90 minutes a day for multiple days immersed in over 2 atmospheres of high pressure inside a hyperbaric chamber.

Wild Plants:

• Plants that are grown in the wild are exposed to more environmental stressors than domesticated plants, which can pass the stress-resilience factors on to you.
• Fruits and vegetables contain polyphenols, phytochemicals, chlorophylls, and cytokines that are released when stressed by animals (xenohormesis) which may offer stress resistance to the animal themselves.
• Learn to identify plants by joining wild-plant foraging groups and if you can’t identify something, don’t eat it. Go to farmers markets to search for wild looking fruits and vegetables. Possibly find an app on your phone.

Hydrogen-Rich Water:

• Purified water infused with molecular hydrogen (H2 gas dissolved in the water). Providing the therapeutic effects of hydrogen, as an antioxidant and cytoprotective effects.
• Shown to produce profound improvement on stem cell availability, decrease the rate at which telomeres shorten, and activate SIRT1 pathways targeted by sirtuin-rich foods such as blueberries and green tea, which results in mitochondrial function. It also increases the expression of antioxidant enzymes in the Nrf2 pathway, indicating that the mild hormetic stress caused by H2 increases resilience in cells stressed with excess oxidation.
• Consumed via tablets, canned hydrogen water, or machines that generate it. Because molecular hydrogen also inhibits NADPH oxidase (NOX), an enzyme that can lower levels of NAD, you can compound hydrogen rich water with NOX inhibitors (pomegranates, blueberries, grapes, green tea, and berberine).

BHB Salts:

• Sodium, potassium, and the ketone body – beta-hydroxybutyrate. Involved in the transcription and upregulation of the enzymes in your body’s natural antioxidant pathways. Also believed to induce ketosis and provide longevity benefits or caloric restriction. They can serve as the primary fuel source for the liver, heart, diaphragm, and other tissues.
• Impaired mitochondrial function often results in excessive production of ROS, which is involved in the development of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancers. Moderate levels of ROS have been shown to protect against chronic disease by upregulating mitochondrial capacity and endogenous antioxidant defenses (mitohormesis). Induced via exercise or dietary modifications, such as the ketogenic diet or anything that increases reliance on mitochondrial respiration. Consuming BHB salts increases the level of ketones beyond what we could naturally produce and enhances antioxidant activity by inhibiting class I and IIa histone deacetylases, regulators that repress the transcription of the FOXO3 gene, a key gene involved in cell autophagy and inflammation. The metabolism of BHB salts also causes a negative redox potential (greater tendency to accept electrons) of the NADP antioxidant system, which can scavenge free radicals.
• Add 1-2 servings of BHB salt to a morning smoothie. Consume before or during a workout mixed with EAAs and electrolytes.

Cold Thermogenesis:

• Cold exposure can cause significant increases in metabolism and calorie-burning, increase insulin sensitivity, reduce systemic inflammation, improve sleep and recovery, and potentially fight certain types of cancers.
• Activates the SNS, which regulates the mobilization and metabolism of stored fat. It also enhances longevity, as does any exposure to hot or cold that mildly stresses the body.

Hyperthermia Therapy:

• Dry sauna, infrared sauna, heating mats, hot tubs, hot springs, sauna suits, or exercise on a hot day. Principally used to treat cancer, but the heart health and cellular resilience processes it triggers make it a strategy for longevity too. Just don’t go too hot for too long or you’ll cause more harm than good. Make sure you are consuming/replacing lost electrolytes.
• Hyperthermic treatment of up to 120 degrees Fahrenheit for a wet sauna and between 158 and 212 degrees for a dry sauna have been shown to cause a significant expression of heat shock proteins (HSP) in muscle. HSP chaperone misfolded or newly synthesized proteins, protect cells from protein misfolding, and strengthen the immune system. The triggering of HSP is also correlated with 30% more muscle regrowth after a week of physical immobilization. Sauna therapy can also increase oxygen consumption and RBC production following exercise, improve stress resistance, and aid in detoxification of chemicals and heavy metals.
• Twice per week, try to get into a dry sauna (170-180 degrees Fahrenheit), wet sauna (110-120 F), or infrared sauna (130-160F) for 15-40 minutes, or until you achieve a noticeable rise in heart rate, sweat production, or both. Focus on breathing or meditating. If these are unavailable, exercise with a few layers of clothing on.

UVA and UVB Radiation:

• UVB enhances health by elevating levels of 25-hydroxyvitamin D, the major circulating form of vitamin D, in people with low baseline levels. Vitamin D is essential for bone, protein, and calcium homeostasis, and a deficiency is associated with an increased risk of age-related chronic diseases, including Alzheimer’s, Parkinson’s, cognitive impairment, and cancer.
• UVA exposure generates nitric oxide, which reduces blood pressure and can act as an antimicrobial.
• Short-term UV radiation induces low-levels of repairable damage to cells and tissues, which triggers short-term bursts of more aggressive cellular maintenance.
• You can get a tanning bed and fit it with a Wolff Dark Tan II Plus light, which combines the highest UVB rating with the lowest UVA rating, or a Collatan Maxi Twist. It is probably better to just get 20-30 minutes in the sun between the hours of 10am-4pm. If your skin burns, you’ve gone beyond healthy hormesis.

3. Caloric Restriction Mimetics

Rapamycin (sirolimus):

• Traditionally used to coat coronary stents, prevent organ transplant rejection, and treat a rare lung disease called lymphangioleiomyomatosis. Rapamycin inhibits excess activation of immune T cells and B cells by reducing their sensitivity to interleukin-2, by inhibiting the mTOR signaling pathway, which is a master regulator of cell growth and metabolism. It is produced by the bacterium Streptomyces hygroscopicus and found on Easter Island (Rapa Nui).
• Known as an antibiotic and immunosuppressant, but in mammals it also targets the mTOR signaling pathway. As DNA or cells become damaged, stimulation of growth pathways in those cells leads to aging and eventually cell death. MTOR pathways, among others, drive this type of aging. By inhibiting these pathways, rapamycin has been shown to help treat certain diseases.
• 0.5-2mg dosage, but it varies because each person has different absorption rates. Blood levels are measured by a medical professional. Can potentially leave you vulnerable to infectious diseases.

Metformin (Glucophage, Glumetza, Riomet, Fortamet):

• Synthesized from the guanidine, which is found in French lilac. It is a activator of the AMPk pathway and is effective at improving glycemic control with a low risk of inducing hypoglycemia.
• Metformin improves glycemic control by inhibiting hepatic gluconeogenesis, which is the liver-based production of glucose from lactate, glycerol, and certain amino acids. It also acts by opposing the action of glucagon. Metformin can improve insulin sensitivity and prevent hyperglycemia-induced aging caused by inflammation and AGE damage caused by elevated blood glucose. It can also reduce inflammation and cell death related to nonalcoholic fatty liver disease, and fibrosis. Finally, it inhibits oxygen consumption in the mitochondria, which can lower metabolism.
• A prescription drug. 1500-2000mg per day for glucose regulation. Could just use a goat’s rue supplement or French lilac tea.
• May cause lactic acidosis, Alzheimer’s, or Parkinson’s with long-term use. Also lowers VO2 max and mitochondrial proliferation. Don’t use it if you have liver or kidney issues. Just take bitter melon extract if you’re desperate to control your blood sugar.

Ketone Esters:

• Exogenous ketones like BHB salts. Ketone esters contain BHB without any salts bound. This allows the body to use the ketones quicker, which raises ketone levels more significantly than MCT oil or BHB salts. HVMN Ketone and KetoneAid KE4 are on the market. When consumed in a drink, the ester bonds are broken down by gut enzymes, releasing butanediol and D-BHB into the blood.
• The same benefits as fasting and ketosis (caloric restriction memetic). The drop in insulin and insulin-like growth factor receptor signaling that happens when you’re in ketosis increases the transcription of genes that encode antioxidant enzymes, such as catalase, glutathione peroxidase, and superoxide dismutase, as well as hundreds of other genes— which makes ketosis an effective method for combating free-radical damage.
• In the presence of high glucose concentrations, ketone esters significantly increase the rate of muscle glycogen synthesis following exercise. Ketone esters can also inhibit NF-kB, a proinflammatory transcription factor that regulates the expression of over 500 genes involved in cellular transformation, survival, proliferation, angiogenesis, inflammation, and more. Inhibiting the NF-kB signaling pathway has been shown to reverse several aspects of aging, e.g., cardiac hypertrophy. MF-kB can block the production of stem cells in older individuals. Downregulation significantly extends life span, memory, strength, skin quality, etc.
• Once per day, preferably in a fasted state, drink a serving of ketone esters. You can also combine it with dextrose or ribose for a potent physical and cognitive performance aid, or with EAAs for long-term stable energy.

Blood Sugar Stabilizing Herbs and Spices:

Bitter melon extract, Ceylon cinnamon, apple cider vinegar, berberine, rosemary, curcumin, fenugreek, Gymnema sylvestre, and capsaicin.

• Bitter melon contains a lectin that lowers blood glucose by acting on surrounding tissues. It also suppresses appetite.
• Ceylon cinnamon lowers blood glucose and reduces inflammation, which contributes to weight gain.
• Apple cider vinegar has been shown to reduce blood glucose levels in diabetic rats, possibly because of its acetic acid restricts the digestion of starch.
• Berberine exerts a hypoglycemic effect, particularly in people with type 2 diabetes, and also lipid metabolism.
• Rosemary has been shown to lower blood glucose, possibly by increasing liver glycolysis.
• Curcumin, the active ingredient of turmeric, and ginger have both been shown to reduce blood sugar levels in diabetic rats.
• Fenugreek seeds reduce fasting blood glucose levels and improve glucose tolerance.
• Gymnema sylvestre helps control blood sugar levels by blocking the absorption of sugar molecules in the intestines.
• Capsaicin reduces blood glucose by increasing insulin.
• Vanadium and chromium are minerals that, taken together, appear to have a blood sugar lowering and insulin stabilizing effect like metformin’s.
• Eat these before or in with high carbohydrate and high protein meals.

4. Sirtuin-Activating Compounds (STACs)

Chemical compounds that affect sirtuins, which are a group of enzymes that use NAD+ to remove acetyl groups from proteins via a process that can allow for proper genetic expression, less protein damage, and extension of life span. Blueberry extract, cacao flavonoids, green tea extract, resveratrol, curcumin, black currants, and fish oil.

Sirtuins influence a wide range of cellular processes, including circadian rhythms, mitochondrial biogenesis, aging, transcription, apoptosis, inflammation, and stress resistance, as well as energy efficiency and alertness during low-calorie situations. STACs are also considered to be caloric-restriction mimetics, and have been shown to help prevent aging-related diseases such as Alzheimer’s type 2 diabetes, and obesity.

A new STAC compound called fisetin, a polyphenol found in tannic drinks, such as tea, wine, and pomegranate juice, and fruits and vegetables, including apples, persimmons, onions, cucumbers, and strawberries. Fisetin is a potent senolytic, meaning it helps in reducing senescent cells, restoring tissue homeostasis, reducing a variety of age-related pathologies, and extending median and maximum life-span. Quercetin (dark leafy veggies, broccoli, red onions, peppers, apples, grapes, black tea, green tea, red wine, and fruit) is an antihistamine and anti-inflammatory compound which can also modulate senescent cell development.

5. Stem Cells and Stem Cell-Supporting Foods

Stem cells are categorized by how many types of cells they can turn into and how they can help with recovery. Those that have accidents and chronic disorders use their stem cell resources up faster for recovery and repair.

Bone Stem Cells:

• There are two primary types of stem cells found in bone marrow: hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Both are tissue specific. HSCs differentiate into different types of blood cells, while MSCs differentiate into bone, cartilage, fat, and connective tissue located in the bone.
• When injected into the body, stem cells usually migrate into tissue and communicate with other cells, such as cytokines and exosomes, to modulate a normal inflammatory or repair response, or to call in other cells for help. Docere Clinics concentrates bone marrow stem cells into a bone marrow aspirate concentrate. This soup is then combined with exosomes and reinjected into any joints that need treatment.

Fat Stem Cells:

• MSCs seem to be similar whether they are taken from bone marrow, adipose tissue, umbilical cord blood, or any other birth tissue. The main difference between fat and bone as sources of stem cells is the number of MSCs that each contains. Adipose tissue apparently contains 500 times more MSCs than bone marrow. Bone marrow also contains more WBCs than adipose tissue, so it may be more inflammatory. Adipose tissue-derived stem cells (ASCs) may also have a higher immunomodulatory capacity than the bone marrow-derived counterparts, which could enhance the potential antiaging effects of ASCs.
• Can be harvested with minimally invasive, low-risk techniques. ASCs – particularly derived from brown fat – can be used to support the new growth of bone cells, liver cells, neurons, vascular endothelial cells, heart cells, and more fat cells.

Amniotic, Umbilical, and Placental Stem Cells:

• Stem cells from umbilical cord blood are not as potent as others. Placentas contain a significant number of MSCs.
• 90 seconds of harvesting amniotic fluid during a cesarean operation. The cells can then be used to support the healthy growth of skin, cartilage, cardiac, nervous, muscle, and bone tissues. Placental cells have shown to have greater immunosuppressive capacity than umbilical cord blood and to proliferate and expand more.
• Using other people’s stem cells is concerning. Better to only use autologous tissue to prevent any diseases being passed.

APSCs:

• Adult pluripotent stem cells. This includes very small embryonic-like stem cells (VSELs), multilineage-differentiating stress-enduring cells (MIAMIs), among others. APSCs have the ability to multiply freely and become any kind of cells in the human body. Unlike embryonic stem cells, they do not have known cancer causing properties.
• Formed in bone marrow and released into the blood stream, where they circulate inactive until your body faces extreme stress, such as low oxygen, low body temperature, or significant injuries.
• Blood is drawn, APSCs are separated and isolated, subjected to very cold temperatures to simulate hypothermia, which activates them. They are then combined with growth factors from your platelet cells and then returned to your body through an IV injection. They then go to work, seeking out areas of inflammation and injury.

Colostrum:

• A concentrated source of proteins, growth factors, and antibodies that are essential for early development of newborns and adults too.
• Richer in antimicrobial peptides, immune-regulating compounds and growth factors than normal milk. It contains low-volume forms of vital nutrients as well as lymphocytes and antibodies, and it helps to balance the gut microbiome and enhances the growth and repair of several tissue types. It also contains cytokines, which keep communication between immune cells active, and growth factors, which assist with maintenance and growth of certain body tissues, including muscle and the gastrointestinal lining. The lactoferrin in colostrum assists with iron absorption and is a crucial part of your immune defense system, and the GH in colostrum works individually and with the other growth factors to aid in the growth and function of the gastrointestinal tissues, muscles, and more.
• Colostrum contains proline-rich polypeptides (PRPs), important immune system regulators that encourage the growth of WBCs and may restore balance in cellular immune functions. PRPs may defend against oxidative stress and support brain health. Studies have now shown that colostrum is a rich source of mesenchymal stem cells. Combined with yeast extract, skullcap, zizyphus (jujube), seaweed, and turmeric had the most therapeutic benefits.
• It can be anabolic (increase IGF-1 and GH), so take it 8 weeks on and 4 weeks off as a powder or capsule. If you have SIBO, colostrum can cause a die off reaction (Jarisch-Herxheimer reaction), so it is important to start with a lower dose if you have gut imbalances.

Algae:

• The chemical structure of chlorophyll is similar to hemoglobin, allowing it to carry oxygen in the blood and increase RBC count. Dried chlorella is about 45% protein, 20% fat, 20% carbohydrates, 5% fiber, and 10% vitamins and minerals. Algal amino acids are unstructured, which means your body can absorb them easily and rapidly.
• Aphanizomenon flos-aquae (AFA), a form of chlorella, affected human stem cells in vitro and in vivo, helping them travel to tissues where they are most needed. Another study demonstrated that spirulina lowered levels of a key neuroinflammatory cytokine in the hippocampus of aged rats, leading to a reverse in cognitive decline and increased neurogenesis. Spirulina protected hippocampal neural progenitor cells from inflammation caused by lipopolysaccharides. Spirulina also promoted mitochondrial respiration and the proliferation of stem cells in culture.
• 100% organic, cracked-cell-wall algae from EnergyBits.

Marine Phytoplankton:

• Produces up to 90% of Earth’s oxygen. Containing essential fatty acids (EPA and DHA), which fuel your brain and nervous system; all amino acids, for muscle, brain, and nervous system support; enzymes and pigments that help eliminate oxidative stress and inflammation; and carotenoids, which play a role in regulating gene expression and inducing cell-to-cell communications.
• The Oceans Alive Raw Marine Phytoplankton has the nanno and tetra forms of phytoplankton. Nanno contains the right balance of amino acids, enzymes, fatty acids, minerals, and pigments, which are the building blocks used to repair DNA, produce glutathione, and generate GHs and stem cells. Tetra has extremely high levels of superoxide dismutase, an extremely powerful antioxidant. It is also high in vitamin C (a strong electron donor) and has been shown to promote deep sleep.

Aloe Vera:

• Contains vitamins and minerals, amino acids, enzymes, lignins, saponins, and salicylic acid. These, along with other steroid-like compounds it contains (steroids, carotenoids, terpenes, and phytosterols) allow aloe vera to modulate various biological activities: it helps prevent cancer, scavenges free radicals, and exhibits antimicrobial activity by rupturing bacterial cell walls. Also shown to improve glucose tolerance and overall glucose metabolism. Aloe vera also improves the viability of dental pulp stem cells, so it may have a significant positive effect on oral health.
• 99% organic aloe, Lily of the Desert and Nature’s Way are 2 good brands.

Coffeeberry Fruit Extract:

• Increases totipotent stem cells and a large amount of antioxidants. In 2 clinical studies it has been shown to significantly stimulate BDNF levels. It also upregulates sirtuin enzymes to offset aging by oxidative stress and support stem cell functions during stress.
• 100% pure Hawaiian coffeeberry extract in a powdered form.

Moringa Extract:

• Antioxidants, natural antibiotic, and the phytochemicals in it are hepatoprotective, cardioprotective, antinociceptive, DNA-protective, and anti-atherosclerotic. Extracts from the flower have shown increases in the proliferation of MSCs, while the root can increase cytotoxicity to cancer cell lines. Extracts from the leaves are known to combat high blood pressure, reduce insulin resistance, reduce inflammation, and reduce the effects of diabetes. It is a member of the sulforaphane family and can increase activity of the Nrf2 pathway that increases cell protection and reduces inflammation and oxidation.

6. Injections

Peptides:

Certain peptides are particularly efficacious for joint healing, mitochondrial support, focus, energy, deep sleep, and longevity. As they can regulate the activity of certain molecules, peptides can influence the body in several ways and act like hormones and neurotransmitters. They’ve been shown to shortcut the protein synthesis process. Meaning, when peptide bioregulators are active, organs can build and tissues can develop easier and faster.

The Peptide Theory of Aging: Changes in the gene expression result in reduced protein synthesis, eventually leading to aging and the development of age-related diseases. By stimulating the body’s own peptide production via peptide bioregulators, specific organs, systems or conditions in the body can be targeted by using a specific short-chain peptide to initiate greater protein synthesis.

• BPC-157 and TB-500 enhance healing and recovery. BPC-157 (body protection compound 157), which protects and heals the gut, is found in trace amounts in gastric juices. It can be taken as an oral supplement or IV near damaged tissues. It also accelerates wound healing and via interaction with the nitric oxide system, protects endothelial tissue and builds blood vessels (useful for IBS).
• TB-500 (thymosin beta-4) is also produced by the human body and promotes wound repair and healing, because it acts on actin and myosin fibers in tendons, ligaments, and muscles. It offers many of the same effects as GH, including muscle growth increase, improved endurance, reduced pain and inflammation, increased flexibility, and increased hair growth. It can act systemically and locally when injected.
• Epithalon is the primary antiaging peptide because it has been shown to activate the telomerase enzyme in humans. Allowing cells to go beyond the Hayflick limit (limited divisions before death).
• Humanin gets produced in unusually high amounts in centenarians, which is encoded in mitochondria and shown to produce strong cyto-protective actions against a variety of stressors and diseases, including oxidative stress, hypoxic damage to the brain, and oxidized LDL cholesterol. It also aids in the repair of mitochondria.
• MOTS-c, is a potent metabolic regulator that significantly decreases the risk of age-related diseases. It activates the AMPK pathway and has an exercise-mimicking effect on fat and muscle. It even induces weight loss in mice fed a high-fat diet.
• When ordering peptides make sure you buy from a trusted and high-quality source such as Peptide Sciences.

Ben’s Protocol:

• Epithalon: He uses the Khavinson protocol, named after Professor Vladimir Khavinson. Professor Khavinson believes the limit of animal and human life span is approximately 30-40% longer than the current mean life span, and that the limit of the human life span is 110 to 120 years. The Khavinson protocol is 10 mg epithalon administered three times a week for three weeks, and that exact dosage was studied in a fifteen-year longevity study in humans that produced impressive results for controlling telomere shortening. The protocol only needs to be done once a year.
• Delta sleep inducing peptide (DSIP): This one needs to be used conservatively to avoid tachyphylaxis (diminishing response to successive doses of a drug, rendering it less effective). He injects 150 mcg three times a week, one hour before bed, and deep sleep levels increase by 30 to 40 percent. This can be continued for as long as it’s needed, as long as it isn’t used every day.
• TB-500/BPC-157: He takes TB-500 at 1.5 mg (0.5 mL) twice weekly for full-body repair. This can be continued as long as desired. For BPC-157, he uses frequent injections of 250 to 500 mcg, and during travel, he relies on the oral tablets from Dr. Seed’s and take four tablets per day.
• MOTS-c: For mitochondrial support, he injects 10 mg once weekly. You can time this just prior to endurance exercise for added mitochondrial benefit, and repeat for up to ten weeks in a row every year.
• FOX04-DRI: FOX04 can sabotage the survival efforts of lingering senescent cells in old tissues, causing them to self-destruct. It has been studied in aged mice and has been shown to cause destruction of senescent cells without the unpleasant side effects of other drugs that do the same thing, while also producing a wide array of benefits that control age-related decline. He takes 3 mg every other day for six days, and repeat this one to three times per year.
• Semax: It’s used mostly in Russia and Ukraine for a broad range of conditions but predominantly for its studied nootropic, neuroprotective, and neurogenic/neurorestorative properties. It can be administered via nasal spray, at one spray (750 mcg) one to three times daily, or whenever cognitive enhancement is desired. He typically combines this with the transdermal cognitive peptide Dihexa.

Thymus:

• From veal, lamb, beef, or pork. The thymus gland’s primary function is to produce T cells. It does this by producing cells called thymocytes, which are precursors to T cells.
• Regulatory T cells maintain immune homeostasis by preventing or limiting T cell activation. They suppress levels of other T cells, including effector T cells, helper T cells, and cytotoxic (killer) T cells. Memory T cells include central memory T cells, effector memory T cells, tissue-resident T cells, and virtual memory T cells.
• Once thymocytes are produced by the thymus, they migrate to peripheral tissues, where they act as the precursors to mature T cells. Supporting your thymus gland can be crucial for longevity and your ability to combat infections. At the age of 60, your thymus is nearly undetectable from surrounding fatty tissue due to age-related deterioration.
• Thymic treatments can be made from thymic extracts from cows or sheep and taken orally or via intramuscular injections. The injectable peptide thymosin-alpha can produce similar T cell enhancing effects. Also epithalon.

Platelet-Rich Plasma (PRP):

Platelets can be administered to a site of pain or injury to supply stem cells, protein, and other growth factors that help to speed up recovery. Blood platelet levels remain fairly stable throughout middle age but past 60 years old, levels fall and continue to decline. Injections of PRP could therefore, have antiaging effects, such as supporting vascular health in older people, reducing age-related joint pain, and preventing normal age-related degradation of the skin and sexual organs.

7. Blood Transfusions

A patient’s plasma, which constitutes 55% of total blood volume, is completely replaced by the blood of a donor over multiple treatments. Rich people taking the blood of healthy young people.

8. Bioidentical Hormone Replacement Therapy

Estrogen can upregulate telomerase and improve mitochondrial health. BHT is a fast track to restoring levels of hormones that naturally decline with age: estrogen, estrone, estradiol, progesterone, testosterone, DHEA, and estriol, as well as growth hormone and insulin growth factor-1.

9. Mitochondrial Support

Nicotinamide Adenine Dinucleotide (NAD):

• A coenzyme produced by all living cells. NAD’s most basic function is to receive and donate electrons during metabolic processes within your mitochondria, making it crucial for normal cellular metabolism.
• NAD is involved in redox reactions, which are processes vital in all parts of cell metabolism. When glucose and fatty acids are oxidized, they release energy. NAD+, the oxidized form of NAD, picks up this energy and is then reduced to NADH during beta-oxidation, glycolysis, and the citric acid cycle. The NADH is transferred into mitochondria, where it is oxidized by the electron transport chain, which is responsible for shuttling protons across membranes and generates ATP.
• NAD+ declines with age, creating an energy deficit that decreases the body’s ability to maintain normal metabolic activity. Leading to more chemical stress, inflammation, DNA damage, and failing mitochondria. By age 50, most people have only half the NAD+ they did in younger years. By 80, NAD+ levels drop to only 1-10%.
• A large dose of NAD supplementation via IV, repeated treatments, an NAD nasal spray or transdermal patch, or daily use of NR, NMN, or NAD supplements. Oral supplements have lower bioavailability and can’t cross the BBB.

Nicotinamide Riboside (NR):

• A form of vitamin B3 and a precursor to NAD. When taken orally, NR is highly bioavailable and aids in mitochondrial energy production. It exists in high levels in cow’s milk.
• Shown to restore NAD+ levels, provide more NAD+ activity than from diet alone, can slow cellular aging, and improve many age-related metabolic problems, including diabetes and neurodegenerative problems.
• NR appears under the name ChromaDex. Tru Niagen, Elysium Basis, and Thorne ResveraCel. One in the morning and one in the afternoon, allowing NR to match the body’s circadian rhythm pulsing of NR.

Astaxanthin:

• A carotenoid that’s produced by single-celled freshwater algae. When their environment becomes stressful due to excessively salty water, low nitrogen levels, or high temperatures, the algae produce astaxanthin in lipid droplets, which turn the algal cells bright red and allow them to survive harsh conditions.
• Astaxanthin protects your mitochondria by acting as both an antioxidant and a free-radical scavenger. It inserts itself into your cell membranes and mitochondrial membranes, where it inhibits free-radical production and helps eliminate the free-radicals that are produced. 14 times more powerful than vitamin E, 54 x greater than beta-carotene, and 65 x greater than vitamin C. It also promotes anti-inflammatory activity and increased production of NK cells. Also, suppressing IL-6 and NF-kB.
• Life Extension has astaxanthin combined with phospholipids to improve absorption. 12mg per day with up to 40mg without negative side effects. A kg of salmon contains between 26-38mg.

Pau D’Arco Tea:

• Beta-lapachone, which acts as acatalyst for NAD.

Curcumin:

• A potent antioxidant and free-radical scavenger that protects cellular function from ROS. Within your DNA are compounds collectively known as the epigenome, which is responsible for maintaining your DNA’s expression and your cell’s identity and function. Over time, your ability to keep your epigenome healthy and functioning declines and genes that used to be inactive may be expressed, and genes that used to be expressed may go dormant. Epigenetic drift may cause stem cell production to decline and increase your risk of cancer and cardiovascular diseases. By reducing inflammatory pathways involved with this downregulation of DNA expression, curcumin can help to prevent epigenetic drift.
• Combining turmeric with black pepper, exposing it to low heat, or combining it with a high quality fat source, such as butter, ghee, olive oil, coconut oil, or avocado oil. 1000mg-1500mg without any negative effects.

Carnosine:

• Made of beta-alanine and histidine. Found in high amounts in skeletal muscle, where it can eliminate excess lactic acid and prevent muscular fatigue. It also promotes mitochondrial and cellular function by acting as an antioxidant and free-radical scavenger. It can reduce the time of telomere shortening and inhibit advanced glycation end products.
• 500-1000mg per day.

Alpha Lipoic Acid:

• A compound derived from sulfur that’s involved in mitochondrial aerobic respiration. Found in cow’s liver, spinach, brussels sprouts, yams, and broccoli. ALA acts as an antioxidant within mitochondria, has free-radical scavenging capabilities, and upregulates your own antioxidant-producing abilities by recycling “used-up” antioxidants like vitamin C and glutathione. Water and fat soluble, it moves through cell membranes and the BBB more easily than other antioxidants. ALA also helps maintain DNA integrity by protecting the epigenome, and it also activates telomerase.
• 200-600mg per day. but does up to 2400mg per day have been taken with no negative side effects. Don’t take with food as it can limit absorption (1-2 hours before a meal).

Apigenin:

• A flavone found in parsley, onions, and oregano, but it is best known as the primary active compound in chamomile tea. Apigenin promotes mitochondrial function by inhibiting the breakdown of NAD, a necessary cofactor in mitochondrial redox reductions.

Sulforaphane:

• Strong anticancer properties and free-radical scavenging, making sulforaphane a strong protector of mitochondrial health. It is also an epigenetic modifier that protects the epigenome and prevents DNA deterioration. It also induces autophagy and stimulates the production of more mitochondria.
• Broccoli sprouts contain high amounts of sulforaphane.

Quercetin:

• A plant-pigment flavonoid found in red wine, white wine, gingko biloba, apples, green tea, St. John’s wort, capers, yellow chili peppers, and onions. A powerful antioxidant. Low concentrations are good but high ones result in creating ROS. 250-1500mg per day.

Epigallocatechin Gallate (EGCG):

• The primary molecule responsible for green tea’s antioxidant effect. More powerful than vitamin E and C, and does not blunt the hormetic response to exercise like they do. EGCG is an epigenetic modifier that protects the epigenome and can improve skin cancer outcomes. It also promotes autophagy, especially in the liver, and in macrophage and endothelial cells. It is known to increase weight loss by increasing fat oxidation. Finally, EGCG crosses the BBB and is highly neuroprotective, reducing inflammation in the brain. 400-500mg per day. A cup of green tea has 90mg.

Fenugreek:

• Regulates blood sugar levels and prevents the onset of diabetes. Fenugreek can mitigate oxidative damage and abate inflammation. It has shown to possess anti-inflammatory capacities that help ease the symptoms of ulcerative colitis, an inflammatory bowel disease.
• The active compound in fenugreek, 4-OH-1le, promotes the production of new mitochondria in diabetic patients, who often suffer from low mitochondria numbers and function.

Fish Oil:

• Both EPA and DHA are precursors of various eicosanoids that are responsible for reducing inflammation. It has been shown to downregulate 41 genes that are involved in aging and decrease the rate at which telomeres shorten. Because fish oil inhibits inflammatory eicosanoids and cytokines, it has been shown to be a beneficial replacement for NSAIDs in the treatment of rheumatoid arthritis.

Coenzyme Q10 (COQ10):

• Found in most aerobic animals, COQ10 is an essential component of the mitochondrial electron transport chain and an antioxidant found in plasma membranes and lipoproteins.
• Found in oily fish like salmon, tuna, and organ meats. 30-90mg per day divided into several doses.

Pyrroloquinoline Quinone (PQQ):

• An antioxidant involved in redox reactions. Helps memory, general cognition, mood, and mental processing power. PQQ also increases mitochondrial density, defense against oxidative stress, improved learning and memory ability, and reduced inflammation.
• PQQ interacts with cell signaling pathways and mitochondria functions. A ROS scavenger. Shown to upregulate compounds that are involved in microglia and hippocampal neuron repair following brain injury.
• Found in kiwis, celery, papaya, sweet potatoes, green tea, fermented bean products like natto, parsley, and even human breast milk.

Glutathione:

• An antioxidant consisted of glutamine, glycine, and cysteine. The depletion of glutathione has been implicated in many chronic diseases, including cystic fibrosis, cataracts, macular degeneration, glaucoma, hypertension, asthma, acute respiratory distress syndrome, Alzheimer’s, Parkinson’s, Huntington’s, myocardial infarction, autoimmune conditions, and even aging itself. The depletion of GSH (the reduced form of glutathione) has also been found to induce the loss of mitochondria function due to the accumulation of damage to mitochondrial DNA. GSH also regulates the release of proteins from the intermembrane space of mitochondria, once released, these proteins engage the machinery of cell death.
• Sublingual supplements seem to get absorbed better (250-1000mg). Vitamin C maintains your body’s supply, selenium is a glutathione cofactor (beef, chicken, fish, cottage cheese), whey protein has a full amino acid profile, and turmeric can help restore levels and improve glutathione enzymes.

Mitoquinone Mesylate (MITOQ):

• Not much evidence but it is supposed to transport CoQ10 to the mitochondria.

Pterostilbene:

• A derivative of the antioxidant phenol resveratrol, but it appears to be a better anticancer and antioxidant molecule. Comes from the peanut skin extract. Peanuts contain antinutrients, lectins, pesticide contamination, and people are allergic. So, maybe just avoid this one.

C60:

• Appears to be a powerful antioxidant. A group of researchers proposed that C60 has the ability to acquire an overall positive charge by absorbing protons and can penetrate the mitochondria to decrease free-radical production. Best dissolved in oil.

Melatonin:

• Acts as an antioxidant, sleep zeitgeber, and mitochondrial protectant. It may delay the development of cancers, boost the immune system, and slow the aging process, as well as improve mitochondrial function. 0.1-0.3mg when required (jet lag).

SKQs:

• Antioxidant compounds that specifically target mitochondria. MitoQ and SkQ both deliver chemical foot soldiers to mitochondria to fight ROS. MitoQ delivers CoQ10, and SkQ delivers plastoquinone. C60 then allows your mitochondria to absorb these compounds via osmosis. So these three molecules—MitoQ, SkQ, and C60—are a mitochondrial stack made in heaven according to Ben.

Urolithin A:

• Urolithin A is produced by the body after you ingest compounds found in particularly high concentration in pomegranates (particularly the bitter components such as the skin and seeds) and can help recycle defective mitochondria. Since it is a metabolite that results from the transformation of the tannins in pomegranate by gut bacteria, it can be classified as a postbiotic.
• In addition, researchers have exposed colon cancer stem cells to a mixture containing urolithin A and found it to be effective at inhibiting the number and size of colon cancer stem cells and also in inhibiting the activity of aldehyde dehydrogenase, a marker of resistance to chemotherapy. Urolithin A can also cross the blood-brain barrier to protect against neurotoxicity and amyloid plaque accumulation.
• As you age, ATP production begins to put strain on your mitochondria, and eventually, energy output falls. But when exposed to urolithin A, these failing mitochondria are broken down and eliminated to make room for new, properly functioning mitochondria to grow.
• Ellagitannins and punicalagins are two natural polyphenols found in pomegranates. They have been shown to have anti-inflammatory and anticancer effects, but once metabolized by gut bacteria, they also produce urolithin A in the digestive tract. So supplementation with pomegranate extract, along with specific bacterial species (probiotics) that can help the pomegranate compounds to produce urolithin A, can be an effective approach to maintaining healthy mitochondria.

Selective Androgen Receptor Modulators (SARMS):

• Therapeutic compounds that mimic anabolic steroids. SARMs contain androgen-like compounds that interact with cellular androgen receptors. The androgen receptor then creates a signal that leads to a magnified expression of particular genes, such as those for muscle growth or fat loss. SARMs are a selective receptor modulator, meaning they can block or activate hormone receptors depending on the conditions.
• Several SARMs produce anabolic to androgenic effects of up to 10 times that of testosterone, without the sex drive fluctuations, gastrointestinal disturbances, stroke, blood clots, and other health issues.
• Cardarine, or GW501516 binds to a PPAR, not an androgen receptor, but despite the difference, it activates AMPK, which is responsible for stimulating glucose intake into skeletal muscle tissue and oxidizing fatty acids. Cardarine can increase HDL cholesterol by an average of 79% while simultaneously decreasing LDL cholesterol. Molecular analyses have revealed that PPAR is involved in exercise-induced reprogramming of muscle fibers and skeletal muscle metabolism by regulating the expression of genes associated with mitochondrial biogenesis and respiration, and since SARMs upregulate PPAR activity, they can be categorized as mitochondrial support. Cardarine has also been shown to cause increased endurance, decreased body fat, and decreased recovery time, and it can also protect the brain, benefit the heart, protect the kidneys, protect against liver damage, strengthen the immune system, and heal skin disorders. 20mg per day, an hour before exercise.

10. Photobiomodulation

Within your mitochondria is an enzyme called cytochrome c-oxidase (CCO), which catalyzes the reduction of oxygen for energy metabolism and ATP production. PBM can increase activity of CCO and also disassociate nitric oxide from CCO, which restores electron transport ATP production by increasing the electrical potential across the mitochondrial membrane. This increased potential is also believed to produce ROS. ROS can exert a mild hormetic effect, leading to increased cellular repair, healing, and gene transcription. This low-level oxidative stress from these ROS may also cause stem cells to grow and proliferate, and the ROS serve as signaling molecules for cell-to-cell communication.

In addition, stem cell proliferation can occur when light-based stimulation of the mitochondria leads to a switch from anaerobic sugar-burning glycolysis to highly efficient oxidative phosphorylation. This switch increases the amount of oxygen that mitochondria require, including those in stem cells, and when these stem cells sense this need for more oxygen, they migrate to tissues with low levels of oxygen that may need enhanced repair.

When it comes to PBM, more is not better: the light frequencies produce ROS, and excessive ROS can cause oxidative damage. The recommended use for the Vielight is one 25 minute session every two days, and for the Joovv, 10-20 minutes per day, but no more.

11. Sulfur Support

One of the most important antiaging pathways in the body is that of the Nrf2 transcription factor, and one of the best ways to support Nrf2 is to eat foods rich in sulfur. Nrf2 is responsible for unzipping and exposing genes that encode for the expression of antioxidant proteins that protect against oxidative damage. Activating Nrf2 switches on a host of antioxidant pathways, increases glutathione production, and can even trigger the expression of an antiaging phenotype. Glutathione acts as a powerful antioxidant within the mitochondrial matrix, and other antioxidants that result from Nrf2-induced transcription also benefit mitochondria in a similar manner.

H2S causes the formation of a disulfide bond between two cysteine residues: cys-226 and cys- 613. The resulting compound deactivates what are called keap1 ubiquitin ligase substrate adaptors. When these adaptors are activated, they cause a chain of events that suppresses Nrf2. So by deactivating these adaptors, H2S creates an environment in which Nrf2 can act freely and promote the transcription of powerful antioxidant genes.

One of the best ways to increase the activation of Nrf2 factors is to consume a lot of sulfur (hence HS2). So fill your diet with plenty of sulfur-containing foods from the Brassica family, which includes bok choy, broccoli, cabbage, cauliflower, horseradish, kale, kohlrabi, mustard leaves, radishes, turnips, and watercress. These foods, along with sulfurous and stinky eggs, onions, and garlic, contain sulforaphane, an H2S-containing compound. Another Nrf2 activator is curcumin. Finally, hydrogen-rich water is also a good way to activate NrF2 pathways.

12. The Aspirin, Magnesium, and Vitamin D Stack

It turns out that daily baby aspirin is associated with a lower risk of heart disease, stroke, dementia, and several kinds of cancer (fish oil can work similarly, with fewer potential side effects). High blood levels of vitamin D are associated with a lower incidence of most cancers, heart disease, and dementia; protection against low bone density and autoimmune disease; and a lower incidence of colds, the flu, asthma, diabetes, stroke, multiple sclerosis, and cognitive decline. Vitamin D’s anti-inflammatory properties likely delay telomere shortening. Higher intake of magnesium helps control blood sugar and retain insulin sensitivity with age.

In addition to eating a wide variety of foods rich in vitamin D, fish oils, and magnesium (including fatty fish like tuna, herring, sardines, and salmon for fish oil; cheese, beef liver, egg yolks, and mushrooms for vitamin D; and avocados, almonds, and Brazil nuts for magnesium), take a daily dose of baby aspirin or fish oil with a dose of vitamin D with your first meal of the day. Dosages range from 1 to 20 g for fish oil and 2,000 to 6,000 IU for vitamin D, depending on your activity levels and size. Ideally, combine vitamin D with 50 to 150 mcg of vitamin K2 to increase its absorption. Then, before bed, take 400 to 600 mg of magnesium.

13. Rhodiola

There is also some speculation that rhodiola may increase stress resilience in a xenohormetic manner, very similar to the extracts from wild plants. One study found that rhodiola consumption is associated with the regulation of the expression of 1,062 different genes, including 72 cardiovascular genes, 63 metabolic genes, 163 gastrointestinal genes, 95 neurological genes, 60 endocrine genes, 50 behavioral genes, and 62 genes associated with psychological disorders, making it a potent supplement for overall longevity and resilience, particularly if you’ve been exposed to radiation.

Rhodiola doses as low as 50 mg are effective in preventing fatigue, and acute doses of 300 to 650 mg are helpful in combating fatigue and stress.

14. Deprenyl

Also known as selegiline, it was developed to treat Parkinson’s disease and Alzheimer’s. It’s most often used with L-dopa to treat Parkinson’s disease, but it may also help prevent the onset of neurodegenerative diseases.

Monoamine oxidase B (MAO-B) is the enzyme responsible for breaking down dopamine, among other neurotransmitters, and MAO-B levels increase as you age. Deprenyl is a selective inhibitor of MAO-B. Twice-weekly doses of 5 mg can help you maintain dopamine levels and high amounts of what I can best describe as positive energy.

15. Telomerase Activators

Telomerase is an enzyme that possesses its own RNA molecule and appears especially significantly in stem cells and cancer cells. It copies its RNA molecule and tacks it onto the ends of your chromosomes, thereby elongating your telomeres and keeping them from fraying or becoming excessively shortened.

Pharmaceuticals:

• Dr. Bill Andrews, the chief scientist of Sierra Sciences and one of the world’s leading experts on telomeres, he told me that he personally uses TAM-818, TA-65 (an astragalus extract), a supplement called IsaGenesis, a vitamin D/K blend, vitamin C, fish oil, and flaxseed oil to maximize telomerase activity. The peptide epithalon is also an effective telomerase activator.

Astragalus:

• It may be able to activate telomerase, but it takes a very large amount of astragalus plant to extract an effective dose. The primary constituent of TA-65 is cycloastragenol, a purified extract of astragalus root. While initial research indicates that cycloastragenol works to activate telomerase, it is still fairly weak: an effective human dosage would be about 1,500 mg per day, but the capsules that are sold currently contain only about 5 to 20 mg and cost several dollars per dose. Because TA-65 is so expensive and possibly too weak, it may be simpler to use astragalus itself in high doses or use a product such as the adaptogenic herb complex TianChi, which contains high amounts of astragalus in a pure, concentrated extraction.
• One of astragalus’s primary effects is protecting mitochondria. Oxidation can damage the lipids that make up mitochondrial membranes, and astragalus inhibits this oxidation. It also been shown to prevent calcium- and oxidant-induced permeation of mitochondrial membranes. Heart mitochondria in particular are protected following astragalus supplementation, which also exerts antioxidant and antitoxin effects on cardiac tissue as well as blood vessels, so the herb can also improve and preserve cardiovascular health. Because astragalus naturally has poor bioavailability, in traditional Chinese medicine, it is often paired with Angelicae sinensis (also known as dong-quai or female ginseng) to increase the absorption of both. The traditional preparation is a 5:1 ratio—30 g of astragalus and 6 g of Angelicae sinensis.

Other Supporting Strategies:

• Ashwagandha, bacopa, boswellia, green tea, horny goat weed, and milk thistle. Other supplements that may stimulate the body to express telomerase include the amino acid carnosine, omega-3 fatty acids from fish oil, curcumin, and resveratrol (found in red wine and grape skin extract). Several varieties of mushrooms have been studied for their ability to increase telomerase activity, particularly in cancerous cells. These include reishi, cordyceps, oyster, shiitake, and wood ear (often listed on mushroom powder and supplement labels as auricularia or auricula). Green tea, oolong tea, coffee, and even being breastfed as a child can all also increase telomere length and telomerase activity. Stress management and even meditation have also been shown to measurably increase telomerase activity. And lifting weights is known to profoundly improve telomere length.

16. Fecal Transplants

Fecal transplants have been shown to be effective in shoving C. difficile bacteria out of your gut and replacing them with the beneficial bacteria that belong there. Fecal transplants have also been shown to be effective in treating some cases of ulcerative colitis, an autoimmune condition characterized by abdominal pain, bloody diarrhea, ulcers on the colon, and fatigue.

Other Strategies:

• Cellular reprogramming: Dr. David Sinclair – cellular reprogramming involves, theoretically at a young age such as 25, delivering a genetically engineered virus into your cells. The virus includes Yamanaka factors, which can cause cells to revert to a youthful, stem cell–like state. Then, when aging sets in later in life, an antibiotic is administered that activates the virus, sparking tissue rejuvenation, organ restoration, chronic disease reversal, and even fading of wrinkles and gray hair.
• Senolytic medicines: Senolytics are a class of drugs that selectively induce death of senescent or aging cells, which are thought to be the root cause and driver of many age-related diseases.
• CRISPR: Currently the simplest, most versatile, and most precise method of genetic manipulation, CRISPR is a technology that enables geneticists to edit parts of the genome by removing, adding, or altering sections of the DNA sequence.
• AI-based drug discovery: The goal of AI-based drug discovery is to shorten the research, discovery, and preclinical stages, from three to four years to just a few months. This could save time and financial resources in the development stage of antiaging drugs, as well as provide stronger drug candidates for approval.
• mRNA: Messenger RNA (mRNA) transfers instructions stored in the DNA to make the proteins required for cells.
• Isotopically fortified organic compounds: Instead of preventing oxidative stress, isotopically fortified molecules do not get damaged by oxidative stress and can be consumed to replace the natural organic compounds that do, making the body more resilient.
• Machine vision and sensing: Advances in AI now allow laser-like accuracy in disease detection from easily accessible data like images. For example, Google Brain has developed accurate predictors for multiple diseases using basic retinal scans. Another company, Haut.AI, uses machine vision to monitor skin health and personalize interventions.
• Wnt pathways: One of primary signaling pathways that regulate the self-renewal and differentiation of adult stem cells are the Wnt pathways, which play a role in the formation of new tissues as well as repair and regeneration.
• New organs: 3-D bioprinting of tissues and organs presents a new way to restore lost tissue structure and function.

Summary:

• Don’t smoke.
• Minimize your intake of processed and packaged foods.
• Be able to clearly identify and succinctly state your life’s purpose.
• Set aside time for friends and family.
• Set aside time to attend to your spiritual disciplines, such as silence and solitude, meditation, gratitude, fasting, or breathwork.
• Have sex regularly.
• Incorporate low-level physical activity throughout your day, and take it outdoors as much as possible.
• Follow a diet low in sugar and vegetable oils and rich in wild plants, dark berries, tannic beverages, herbs, spices, sulfur-rich foods, organ meats, healthy fats, and low-glycemic-index carbohydrates such as legumes and tubers. If you carry genetic factors that predispose you to excess fat storage, an inflammatory response to fats, or difficulty digesting fats, continue to incorporate regular periods of fasting and manage your blood glucose, but shift toward a more Mediterranean approach higher in monounsaturated fats (see chapter 13 for more on this).
• Perform a 12-16 hour intermittent fast every day, a 24 hour dinner-to-dinner fast 1-4 times per month, and a caloric-restricted or zero-calorie 3-5-day water fast 2-4 times a year.
• Drink pure, clean, filtered water and add liquid trace minerals, sea salt, or Celtic salt to it. Also include hydrogen tablets or some other form of hydrogen-rich water at least twice a day, in the morning and evening, if your budget permits.
• Each day, expose your body to a variety of hormetic stressors, e.g. cold, heat, sunlight, wild plants, herbs, hyperoxia, and hypoxia (use a hyperbaric chamber or LiveO2 if either fit your budget). Consider supplementing with ketone esters or ketone salts, particularly for long fasting periods, before or after airline travel, or before or during long workouts.
• Prior to any carbohydrate  meal, consume insulin-stabilizing compounds such as bitter melon extract, Ceylon cinnamon, apple cider vinegar, berberine, rosemary, turmeric, ginger, fenugreek, Gymnema sylvestre, or cayenne.
• Consume a variety of shellfish and organ meats, including sweetbreads (thymus), liver, heart, and kidneys, at least four times a month. If you wind up leaving out the sweetbreads, consider using the peptide epithalon, the peptide thymosin-alpha, or thymus injections.
• If your budget permits, consume a morning or midday smoothie that contains rhodiola, colostrum, chlorella, spirulina, marine phytoplankton, aloe vera, coffeeberry fruit extract, frozen broccoli sprouts, and moringa. You can also include other sirtuin-supporting foods in the smoothie, such as blueberries, cacao powder or cacao nibs, black currant powder, turmeric, quercetin, chamomile, or green tea extract.
• Increase telomerase activity by consuming one packet of TianChi on an empty stomach at some point in the afternoon, or by supplementing with astragalus or TA-65 and TAM-818.
• If your budget permits, supplement each morning with carnitine, alpha lipoic acid, CoQ10, PQQ, glutathione, pterostilbene, MitoQ, astragalus, vitamin D, fish oil, C60, SkQs, and a good multivitamin/mineral complex, and then supplement each evening with magnesium, melatonin, and, if you are not breastfeeding or having regular sex, oxytocin. Also try to use a daily probiotic that contains pomegranate seed and skin extract (such as the brand SEED).
• The prescription drugs rapamycin, metformin, and deprenyl are not recommended.
• If your budget permits, at some point during the day, consume a serving of ketone salts or ketone esters.
• If your budget permits, purchase and regularly use a Vielight, Joovv light, and a low-EMF infrared sauna.
• If your budget permits, get an NAD IV once a month and sustain levels with daily NR or NMN intake or NAD patches between IVs. Alternatively, and especially for an affordable solution, prepare and drink pau d’arco tea daily.
• If your budget permits, harvest and bank your stem cells and, one to two times per year, have them injected into any ailing joints or into your bloodstream, preferably combined with PRP and exosomes.
• If your budget permits, visit an antiaging or wellness clinic monthly or quarterly for thymus and placental injections, along with a test of your hormones so you can consider bioidentical hormone replacement therapy if needed.

How to Quantify Aging

Resting Heart Rate

Telomere Testing:

Relatively new laboratory technology can measure the rate at which telomeres shorten, along with mitochondrial aging, white blood cell count, cellular damage, and more. At-home testing companies such as TeloYears, SpectraCell, Repeat Diagnostics, and Life Length can use this technology to measure your average telomere length (ATL). ATL is the mean length of all telomeres in a given sample of leukocytes or white blood cells found in a single drop of blood

White Blood Cell Count:

WBC counts on the lower end of normal can predict a better chance of a long life. This seems to be true primarily in healthy individuals, and people who are generally unhealthy or have a compromised immune system should not use low WBC counts to predict longevity. The normal range for WBCs is 4,000 to 10,000 cells per microliter of blood.

Handgrip Strength:

Grip strength is known to predict all-cause mortality risk in middle-aged and elderly people even better than blood pressure. Even when controlling for disease status, inflammatory load, inactivity, nutritional status, and depression, grip strength predicts all-cause mortality in older disabled women, and poor grip strength is an independent risk factor for type 2 diabetes.

Walking Speed:

People who walk the fastest tend to die later. A study performed in 2013 revealed that out of seven thousand men and thirty-one thousand women who walked recreationally, those with the highest frequent natural walking speed were less likely to die than others. Conversely, a rapid decline in walking speed has been shown to predict death.

Facial Appearance

Subjective Evaluation of Your Quality of Life

Muscle Quantity (with a Caveat) and Quality:

Since muscle produces proteins and metabolites that directly regulate your recovery from trauma and injury, lean muscle mass can serve as a metabolic reservoir for healthy aging. Some research suggests that the more muscle you have, at least to a certain extent, the better you can recover from surgeries, burns, falls, breaks, and punctures, and the longer you can stave off sarcopenia. Muscle is also directly correlated to longevity because the expression of a longevity-enhancing protein known as kiotho depends on skeletal muscle strength. The only caveat is that it must be high-quality, functional, powerful muscle (no need for excess maintenance and cooling).

The fat-free mass index (FFMI) is an excellent measure of muscularity. Your FFMI is equivalent to your lean body mass in kilograms divided by your height in meters squared. The equation looks like this:

• FFMI = (lean body mass in kg) ÷ (height in m)2

The average FFMI score for men is about 19, and the average score for women is about 15.

Life Purpose:

Having a strong life purpose predicts your allostatic load (wear and tear), and that people with a stronger life purpose tend to live longer than those who have no clear direction or purpose in life. Make sure that you can express your purpose in one succinct sentence, and if you need help figuring it out, check out Mastin Kipp’s book Claim Your Power.

Intelligence:

An aspect of intelligence-induced longevity may be that more intelligent people make more intelligent decisions regarding their health, choosing healthy behaviors over self-destructive ones. Basically, the smarter you are, the less likely you are to drink too much, not exercise, overeat fast food, or smoke.

Aging Clock Analysis:

Part of the nucleolus is occupied by ribosomal DNA (rDNA), which encodes for RNA. There appears to be a direct link between nucleolus aging and markers of accelerated aging in humans, and researchers now hypothesize that measuring the amount of methylation on the rDNA may turn out to be a very accurate way to determine true biological age. But at this point, rDNA measurements aren’t widely available or cost effective.

The Bottom Line

• Track your resting heart rate daily.
• Get a telomere test, CBC, and mitochondrial profile test annually.
• Get a body fat test quarterly.
• Test your handgrip strength weekly.
• Pay attention to the way your face looks in the mirror weekly.
• Perform a treadmill walking speed test weekly (you can do this as a warm-up or cool-down for any of the workouts from chapter 12).
• If you own a device that tracks muscle speed and power, choose one strength training workout from chapter 12 during which you can measure muscle speed production, or simply keep mental or written track of your strength progressions for specific exercises, and try to track on a monthly basis.
• Take a subjective quality-of-life questionnaire.
• Create a clear, short, succinct, one-sentence purpose-of-life statement, memorize it, and put it into action.

Avoiding Baldness, Grays, And Wrinkles

Skin, Joints, Bones, And Gut Lining with Collagen

80% of collagen is type 1, 2, and 3. Type 1 and 3 provide structure for your skin, muscles, and ligaments, while type 2 is found in cartilage and your eyes. Collagen makes up 80% of your skin and is found in the middle layer called the dermis. It works together with elastin to strengthen the skin and help it snap back when stretched.

At about age 25, you start breaking down more collagen than you build and lose about 1% each year. Excess sun exposure, smoking, too much UV light exposure.

Collagen protein powder is hydrolyzed, meaning it’s been partially broken down into the main amino acids that your body needs to produce more collagen: glycine, proline, and hydroxyproline.

Helping joint health, skin elasticity, intestinal lining, glycine helps produce stomach acid, therefore digestion.

Heart burn is caused by not enough stomach acid. It causes the esophageal sphincter to open until there is enough stomach acid to break down and sterilize food.

Glycine is also an inhibitory neurotransmitter, which calms the nervous system and can improve sleep.

The body also needs vitamin C to produce collagen. It is a powerful antioxidant, so it protects your skin cells from free radicals that break collagen down and it helps to assemble amino acids into collagen.

Cryotherapy:

• Increases collagen production and blocks inflammatory enzymes and hormones that destroy collagen. Temperature drops can also increase glutathione and superoxide dismutase production.
• Cold exposure helps mitochondria and stimulates capillary beds to increase circulation in your skin. Mitochondria change cardiolipin levels, which are a component of the inner mitochondrial membrane, so they can produce heat more quickly.

Microneedling:

• Disrupts collagen and stimulates the body to form new, youthful collagen fibers. You can also combine this with platelet-rich plasma (PRP) in a treatment called vampire facials. Your blood is separated from plasma, which contains growth factors, then it is applied to the face before and after microneedling to further stimulate the growth factors. Good for healing acne scarring.

Retinol:

• Pure vitamin A. Retinoic acid purges old skin cells and causes new, healthy cells to form quickly, increasing collagen production. It makes your skin more sensitive to UV light and may burn if you already have sensitive skin though. Bakuchiol can mimic the activity without negative effects.

Methylene Blue:

• A powerful cognitive enhancer and acts as a mitochondrial antioxidant. It can also delay connective tissue aging.

Laser Facials:

• Remove surface layers of skin.

Melanin:

• Alpha-melanocyte stimulating hormone stimulates melanin production and is also an anti-inflammatory hormone, which people with autoimmune conditions and toxic mold exposure have low levels of. Consume extra polyphenols.

The Longevity of Your Hair

As we grow older, catalase production decreases and we don’t have enough to break down hydrogen peroxide that our hair follicles produce, damaging melanocytes. Glutathione can also help break hydrogen peroxide down. Ashwagandha, curcumin, saw palmetto, and vitamin E can ramp up catalase production.

A shortage of MITF (a gene which is attacked during stressful infections) triggered the immune system to further attack melanocytes, leading to gray hair.

Too much DHT causes hair follicles to shrink, leading to baldness. Mitochondrial dysfunction may cause baldness too.

Stress, toxins accumulating in the liver, hormonal imbalances, inflammation, and free radicals affect T3 and progesterone, which modulate mitochondrial activity. Cortisol inhibits TSH, which inhibits the production of T4, which must be converted into T3 to be used. Without enough T4 or the energy to convert it, it gets converted into the inactive reverse T3 instead. Symptoms of low thyroid function include hair loss and may be found with a T3/RT3 test. Stress causes your body to make more RT3, less T3, and mitochondria can’t produce enough energy.

Thyroid hormone disruption can also cause the stem cells in the hair follicle to bulge since they can’t be activated by T3.

Danshen upregulates Wnt, which allows the signal from thyroid hormones to stimulate the production of new hair follicles.

High levels of RT3 and not enough T3 leads to downregulation of progesterone, which causes estrogen dominance. With disrupted estrogen levels, you don’t make collagen efficiently.

Do these things for skin:

• Grass-fed or pastured collagen protein (10g per day)
• Eat more foods containing polyphenols and antioxidants: vegetables, coffee, tea, and chocolate. Vitamin C too
• Cryotherapy, microneedling, and retinol, copper peptides, and methylene blue
• Yellow light therapy

Do these things for hair:

• Avoid phthalates, parabens, and benzophenones. Consider avoiding birth control pills
• To avoid grays, ramp up catalase production by taking antioxidants like ashwagandha, curcumin, saw palmetto, and vitamin E
• Try a DHT blocking shampoo for baldness
• Deal with stress
• If you are balding prematurely, get thyroid levels checked by getting a RT3/T3 levels test
• To stimulate blood flow to the scalp, get a head massage

Metabolic Autophagy

The Hallmarks of Aging

• Genomic Instability – genetic damage and mutations throughout life
• Telomere Attrition – shortening of protective telomere caps on top of chromosomes that occurs during DNA repair
• Epigenetic Alterations – alterations in methylation patterns, post-translational modification of histones, and chromatin remodeling
• Loss of Proteostasis – dysfunctional protein folding, proteolysis, and proteotoxicity. Basically, not being able to put muscle back together correctly.
• Deregulated Nutrient Sensing – inadequate growth hormone production, related to the Insulin/IGF-1 signaling pathway
• Mitochondrial Dysfunction – old worn-out mitochondria begin to produce more reactive oxygen species and oxidative stress, which damages all other cells
• Cellular Senescence – the accumulation of dead cells and cancer proliferation
• Stem Cell Exhaustion – decline in regenerative potential of tissues and lack of swapping old cells with new cells
• Altered Intercellular Communication – miscommunication in endocrine, neuroendocrine, or neuronal systems that cause inflammation and other problems

Biological organisms develop certain adaptations based on the conditions they get exposed to in their environment. That’s why some animals have completely different metabolic profiles as well as physical traits than humans. They also live differently partly because of how they’ve adapted to their surroundings over the course of eons. That’s why most of these hallmarks of aging are controllable and epigenetic. You can influence your rate of aging and longevity by simply understanding these mechanisms and changing your lifestyle.

Mitochondrial Theory of Aging

In 1956, Denham Harman was the first to propose the Free Radical Theory of Aging (FRTA and furthered the idea in 1970 to describe mitochondrial production of reactive oxygen species (ROS). The free radical theory of aging states that organisms die because of the accumulation of free radical damage on the cells over time.

The classical free radical theory of aging proposes that energy generation by the mitochondria damages mitochondrial macromolecules, including mitochondrial DNA (mtDNA), which promotes aging. After a certain threshold, this produces too many reactive oxygen species (ROS), which cause cell death and degradation. This happens when electrons get out of the electron transport chain and react with water to create ROS, such as superoxide radical. These radicals damage DNA and other proteins.

Age-related impairments in the mitochondrial respiratory chain decrease ATP synthesis, damage DNA, and make the cells more susceptible to oxidative stress. However, it’s been shown that mutations in mtDNA can result in premature aging without increasing ROS production by mutating the polymerase Pol-γ that’s responsible for mitochondrial DNA synthesis.

Excessive generation of ROS and mutations in mtDNA are both central to the mitochondrial theory of aging. However, it’s suggested that ROS aren’t the primary or initial cause of it.

Reactive Oxygen Species and Aging

Mutant mtDNA increases with age, especially in tissues with higher energy demands like the heart, brain, liver, kidneys, etc.

In some species like yeast and fruit flies, reducing oxidative stress can extend lifespan. However, blocking the antioxidant system in mice doesn’t shorten lifespan in most cases. Taking a lot of antioxidants and lowering oxidative stress with supplements have failed to be effective in fighting disease and in fact may promote the chances of getting sick. Treatment with high doses of anti-oxidants like beta-carotene, vitamin A, and vitamin E may actually increase mortality. Consuming more fruit and vegetables doesn’t seem to have a significant effect on reducing cancer risk. Increasing your body’s own endogenous antioxidant levels may be a better option for disease prevention.

Sublethal mitochondrial stress with a minute increase in ROS may cause a lot of the beneficial effects found in caloric restriction, intermittent fasting, exercise, and dietary phytonutrients.

• If you experience no stress and zero exposure to free radicals, then your body is by default weaker because of having no fighting reference from the past.
• If you experience too much stress and excessive accumulation of ROS, then you promote disease and sickness because of not having enough time to recover.
• If you experience just the right dose of stress, then you’ll be able to deal with it, recover from the shock, and thus augment your cells against future stressors.
• If you block all mitochondrial stress and eliminate free radicals, then your body won’t have the time nor the means to promote mitohormesis. That’s why antioxidants all the time won’t have a positive effect.

Here are some of the factors that have been shown to produce oxidative stress and induce mitochondrial aging:

• Insulin and high glucose environments generate free radicals and promote oxidative stress. The insulin signaling pathway is one of the main mechanisms of accelerated aging. However, this is dose specific and some is beneficial for ROS production.
• Chronic stress accelerates aging and disease. Over-production of free radicals due to excessive stress hormones decreases mitochondrial functioning and makes you more prone to disease because of a weakened immune system, high insulin, and damage to cells.
• Sleep deprivation and circadian rhythm disruption promotes all disease. If your body’s biological clocks are misaligned with its circadian rhythms, then you’ll cause more cellular stress and predispose yourself to all types of dysfunctions.
• Avoid environmental toxins and pollution. Polluted air, water, heavy metal exposure, mercury in food, pesticides, glyphosate, GMO crops, toxic personal care products, house cleaning chemicals – all of them will create more reactive oxygen species and oxidative stress. The amount of these stressors is beyond our body’s natural ability to cope with them; thus, they don’t have a beneficial effect in the long run.
• Avoid inflammation. Inflammation is correlated with most diseases, as it directly decreases the body’s immune system function. Processing food and over-cooking it increases the number of free radicals and carcinogens in it.

Longevity Pathways in Humans

The Growth Hormone/Insulin and Insulin-Like Growth Factor-1 Signaling Pathway, which regulates cell replication, nutrient partitioning, and storage:

Insulin is the main storage hormone that directs nutrient partitioning and glycogen replenishment. It basically helps to unlock the cells so they could store glucose into liver and muscle glycogen.

Insulin-Like Growth Factor (IGF-1) or somatomedin C is an IGF- 1 encoded human gene. It’s also been referred to as the ‘sulfation factor’. IGF-1’s role is to promote tissue growth and development.

• The effects of IGF-1 are mediated through the IGF-1 receptor (IGF-1R), which is similar to the receptor of the storage hormone insulin.
• IGF-1 gets produced in the liver by the stimulation of Human Growth Hormone (HGH). IGF binding protein (IGFBP) is a binding protein that carries IGF-1 around the body and it’s regulated by insulin.

Caloric Restriction and Longevity:

Caloric restriction and energy deprivation lower mTOR signaling, which in turn upregulate other pathways of energy homeostasis, such as AMPK and autophagy.

The life-extension benefits of caloric restriction and fasting are mostly induced by autophagy and increased sirtuin activity that promote cellular turnover and recycling of old cells.

The life cycles of mitochondria are characterized by fission and fusion events:

• Fusion states happen when several mitochondria mix and organize themselves into a network. They basically merge together into a single much larger mitochondrion.
• Fission states happen when the fused mitochondria get split into 2 out of which the one with a higher membrane potential will return to the fission-fusion-cycle and the one with a more depolarized membrane will stay solitary until its membrane potential recovers. If its membrane potential remains depolarized it’ll lose its ability to fuse and eventually will be eliminated by mitophagy.

Changes in nutrient and energy availability can make the mitochondria stay in either one of these states for longer:

• Post-Fusion State is called Elongation, which is characteristic to states of energy efficiency, such as starvation, acute stress, caloric restriction, and biological aging (senescence).
• Post-Fission State is called Fragmentation, which shortens the mitochondria and keeps them separate. This is typical to bioenergetic inefficiency that’s caused by high energy supply and extended exposure to excess nutrients.

Basically, caloric restriction promotes energy efficiency because the organism is required to sustain itself with fewer calories. Having access to an abundance of energy, however, leads to inefficient mitochondrial function because every single mitochondrion must expend less effort to carry its weight. That can lead to the accumulation of dysfunctional components.

Caloric restriction shows increased lifespan of brain neurons in both humans and monkeys. One human study on 3 weeks of alternate day fasting discovered an increase in SIRT1, which is associated with longevity. It’s suggested that caloric restriction induces cellular respiration, which increases NAD+ and reduces NADH levels. NADH inhibits Sir2 and SIRT1.

SIRT1 has been shown to also activate PGC-1α, which triggers the growth of new mitochondria. SIRT3, SIRT4, and SIRT5 improve mitochondrial function as well.

When your body faces a shortage of energy, then you’re going to promote the fusion of mitochondria. This lowers your energetic demands because the organelles in your cells are better connected. It’ll also make you recycle old worn-out cell components and convert them back into energy through the process of autophagy.

Energy restriction also upregulates the other genes that increase energy efficiency by improving insulin sensitivity and fat oxidation. During states of fasting or depletion of exogenous calories, your mitochondria rev up their functioning and boost endogenous energy production from internal sources.

Ketosis is another vital component to the survival of the mitochondria as it allows them to become more energy efficient. This shift of starting to burn ketones preserves muscle tissue, gives adequate energy to the brain, and keeps you satiated by downregulating some of the hunger signaling.

The mitochondrial fission-fusion cycles are also dependent on autophagy modulating pathways such as AMPK and mTOR:

• mTOR or mammalian target of rapamycin is responsible for cell growth, protein synthesis, and anabolism. It will make the body build new tissue.
• AMPK or AMP-activated protein kinase is a fuel sensor that is involved in balancing energy deprived states.
• Autophagy is the process of self-eating and cellular turnover in which the body recycles its old worn-out components back into energy.

mTOR inhibits autophagy because it makes your body grow, which requires expending energy and upregulating the metabolism, whereas AMPK supports autophagy due to the energy-deprived state.

Nutrient starvation allows unneeded proteins to be broken down and recycled into amino acids that are essential for survival. That keeps the organism alive longer because of increased mitochondrial efficiency. Therefore, the key to longevity and increased lifespan still gets traced back to decreased energy intake and improved energy usage within the body itself.

The FOXO/Sirtuin Pathway, which includes proteins and transcription factors responsible for energy homeostasis. They manage homeostasis under harsh conditions and stress:

Sirtuins are a family of proteins that act as metabolic sensors. They deacetylase the coenzyme NAD+ into free nicotinamide. Basically, they break down acetyl from proteins to maintain their functioning for longer. The ratio of NAD+ to NADH determine the nutritional status of the cell, and sirtuins are there to respond.

NAD+ is an essential currency for energy metabolism and DNA repair. Sirtuins are proteins that evolved to respond to the availability of NAD+ in the body.

Cellular deterioration and senescence are thought to be caused mostly by the accumulation of unrepairable DNA damage. SIRT1 plays an important role in activating DNA repair proteins. It’s specifically involved with repairing the double helix of DNA. SIRT1 can also induce cellular autophagy by directly deacetylating AuTophaGy (ATG) proteins such as Atg5, Atg7, and Atg8. This then promotes mitophagy or mitochondrial autophagy and helps to eliminate old worn-out cells.

How to increase sirtuins for longevity:

• Glucose restriction extends the lifespan of human fibroblasts because of increased NAD+ and sirtuin activity. Inhibiting insulin shuttles SIRT1 out of the cell’s nucleus into the cytoplasm.
• Caloric restriction and fasting increase SIRT3 and deacetylate many mitochondrial proteins.
• Activating AMPK elevates NAD+ levels, leading to increased SIRT1 activity. AMPK is the fuel sensor that mobilizes the body’s energy stores such as fat and it promotes autophagy as well.
• Ketosis and ketone bodies like beta-hydroxybutyrate (BHB) are associated with increased sirtuin activity.
• Exercise has anti-inflammatory effects and it increases SIRT1.
• Cyclic-AMP (cAMP) pathway activates SIRT1 very rapidly to promote fatty acid oxidation independent of NAD+. cAMP is linked with AMPK which gets activated under high energy demands while being energy deprived.
• Heat exposure and saunas increase NAD+ levels which promote SIRT1 as well. Sweating, cardio, yoga, or infrared saunas will probably have a similar effect on activating heat shock proteins.
• Chronic oxidative stress and DNA damage deplete NAD+ levels and decrease sirtuin activity. This will then disrupt DNA repair and impair mitochondrial functioning. That’s why you want to keep stressors acute and followed by recovery.
• Melatonin can activate sirtuins and has anti-aging effects.
• Sirtuins also affect the circadian clocks so keeping a consistent circadian rhythm is incredibly important for longevity. NAD+ is under circadian control and when you’re misaligned, you’ll have less energy and lower SIRT1 and SIRT3 activity. Circadian rhythm mismatches are linked to many metabolic disorders, glucose intolerance, and brain degeneration.

Hormesis and General Stress Adaptation Mediated by FOXO Proteins and Mitochondrial Functioning:

This phenomenon makes the organism more resilient against environmental stressors.

Exposure to stress whether that be the cold, caloric deprivation, or the heat makes the organism live longer because of forcing hormetic adaptation. 

Increased insulin/IGF-1 signaling mutations prevent the localization of DAF-16 by heat shock, which raises the possibility that the increased lifespan due to stress adaptation occurs because of lower insulin.

Increase FOXO Factors for Longevity:

‘FOX’ stands for ‘Forkhead box’ and it represents a class of proteins and transcript factors that have many functions in the human body. FOXO proteins are transcript factors that regulate longevity through the insulin and insulin-like growth factor signaling.

Invertebrates have a single FOXO gene, whereas mammals have four: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, FOXO proteins regulate stress resistance, cellular turnover, apoptosis, glucose and lipid metabolism, and inflammation.

FOX represents the class of proteins, the letter ’O’ is the subclass, and the number represents the member of that group. There are over 100 subclasses of FOX proteins in humans, such as FOXA, FOXR, FOXE, etc. and they have many functions. FOX proteins with the class ’O’ are regulated by the insulin/Akt/mTOR signaling pathway.

Theoretically, upregulated FOXO pathway activities increase lifespan in many species because of promoting stress adaptation in harsh environments. The FOXO pathway is an evolutionarily viable mechanism for adapting to low levels of insulin and energy deprivation.

Anabolic mechanisms such as insulin, mTOR, and IGF-1 tell the body to grow and replicate but this may come at the expense of longevity and accelerated aging. Which is why you’d want to know how to balance it with the catabolic processes of autophagy, AMPK, and FOXO factors.

SIRT1 increases FOXO DNA binding by deacetylating FOXO in response to oxidative stress. FOXO proteins get increased in response to cellular stress and increased energy depletion.

• Calorie restriction increases sirtuins as well as FOXO factors.
• Fasting for 48 hours elevates FOXO1,3, and 4 by 1.5-fold and refeeding drops it back to baseline. FOXO1 is also critical for adapting to fasting by activating. gluconeogenesis in the liver. This makes the liver produce its endogenous glucose whether from amino acids or fatty acids.
• Even just acute exercise increases FOXO1 phosphorylation, improves insulin sensitivity and promotes mitochondrial biogenesis. However, chronic exercise may decrease this exercise-induced FOXO expression.
• In response to heat stress, Drosophila dFOXO contributes to increased heat shock protein levels, which will protect DNA damage and maintains cellular resistance. Taking a sauna, exercising and sweating can promote FOXO activation.
• Exposure to cold stress before heat stress lowers FOXO translocation in fruit flies but it doesn’t compromise longevity and resistance to the heat. Cold exposure actually can boost longevity and lifespan.
• FOXO3a is activated in response to hypoxic stress and inhibits apoptosis.

The general trend for increasing FOXO follows the same pattern as the other longevity pathways such as AMPK and Sirtuins. Energy deprivation and adaptation to stress make the organism more resilient and longer lived. It forces the body to continue producing energy and survive in situations of low nutrients, thus becoming really efficient at its own metabolic processes. Being chronically taxed out and under harsh conditions will inevitably lead to an accelerated deterioration just because of the accumulated damage. The cells themselves react to this by looking at the functioning of telomeres.

Telomeres and Longevity:

The sequence of telomeres is TTAGGG, which gets replicated over 2500 times in humans. In order to keep the organism alive, chromosomes are continuously replicating themselves and repairing DNA. Every bout of chromosome duplication causes a shortening in telomeres because the enzymes involved in duplicating DNA can’t continue their duplication all the way to the end of a chromosome. So, telomeres are vital protective caps that are supposed to protect the genes from damage during this process.

Telomere shortening prevents cells from replicating themselves by limiting the number of cell divisions. Shortened telomeres also weaken the immune system, increasing the risk of cancer.

On average, human telomeres shorten from about 11 kilobases as a newborn to less than 4 kilobases in old age.

Telomere length can be replenished by an enzyme called telomerase reverse transcriptase (TERT). TERT is a subunit of Telomerase which adds TTAGGG sequences to the ends of chromosomes.

• Telomerase activity can prevent the shortening of telomeres that occurs with aging. Telomerase is responsible for the self-renewal properties of stem cells by elongating the telomeres of stem cells, which prevent telomere shortening and increase the lifespan of stem cells.
• Telomerase is more active in rapidly dividing cells such as embryonic stem cells and adult stem cells and they’re quite low in neuronal, skin, pancreas, adrenal, cortex, kidney and mesenchymal stem cells.
• Telomerase activity determines how many times a cell can divide before it dies off completely. It takes about 30-50 cycles of replication until the cell becomes senescent and dead.

Although telomere shortening is linked to aging, over-expression of TERT can promote cancer and tumor formation. Telomerase activity can immortalize cancer cells and about 90% of cancers are characterized by increased telomere activity.

Telomeres are highly susceptible to oxidative stress and stress-mediated DNA damage is a huge contributing factor to telomere shortening. Too much stress shortens telomeres but it also damages the mitochondria. That’s why a healthy lifestyle should include active stress management. Here’s how to increase telomere length and prevent telomere shortening:

• Meditation helps to maintain telomere length and protect them from getting damaged. It increases telomere activity and reduces oxidative stress. Meditating lowers psychological as well as physiological stress and boosts the immune system.
• Intermittent fasting can promote telomere activity and function through several mechanisms. It lowers oxidative stress, removes senescent cells through autophagy, and boosts stem cell production.
• Resistance training and muscle building slow down aging. As you age you decrease the number of satellite cells that are precursors to skeletal muscle cells and you lose muscle mass. Shortening of satellite cell telomeres prevents satellite cell replication and contributes to age-related sarcopenia

The mTOR/AMPK Pathway, which governs homeostasis between anabolism and catabolism. 

Hormesis and Longevity

Hormesis is a biphasic response to a toxin or a stressor. (1) The initial contact causes injury to the body. (2) The following reaction leads to adaptation, leaving the body in a better condition than it was before. In 2012, Mark Mattson explained that cells respond to bioenergetic stressors by increasing DNA repair proteins, antioxidant enzymes and the production of neurotrophic factors (such as BDNF). It’s also believed that this is the reason eating vegetables, tea or coffee can improve brain health.

• Plants contain ‘noxious’ chemicals that are supposed to protect them from being eaten by insects and other organisms.
• However, thanks to the constant evolutionary arms race between us and animal kingdom, we’ve developed counter-adaptations in the form of hormesis and we trigger a beneficial response when eating these foods.

Examples of Hormesis:

• Physical exercise. It triggers adaptations that increase mitochondrial density and biogenesis through mitochondrial hormesis.
• Alcohol is another hypothetical form of hormesis as it’s believed to prevent heart disease and stroke. However, there’s evidence to show that these benefits are exaggerated.
• Red wine contains resveratrol, which is one of those protective plant compounds and it’s greatly associated with anti-aging effects (1-2 glasses a week). Still a neurotoxin though. Benefits are very exaggerated and the amount you would need to drink to obtain these benefits would cause way more harm.
• Exposure to Sunlight at low or moderate doses has a lot of health benefits. It’s one of the most effective ways of synthesizing Vitamin D in the body but it also supports most metabolic processes.
• Cold Exposure triggers AMPK, which causes your mitochondria to grow and improve their efficiency. It’s also a positive adaptation to lower temperatures with many other health benefits, such as reduced inflammation, stronger immune system, and greater tolerance to pain.
• Heat Exposure activates these so-called ‘heat shock proteins’, which allow the cells to resist the damaging effect of heat. High temperatures can also stimulate the lymphatic system, which works like an inner pump for moving liquids and toxins in the body.
• Caloric Restriction and Intermittent Fasting cause mild oxidative stress that trigger protective sirtuin proteins. Short-term fasting and starvation can also fight cancer and make cancer patients more resilient against chemotherapy.
• Mental Stress is another example of hormesis where you’re forced to flex your neural muscles. Learning new things, gaining skills, being in unpredictable high-stress situations, novel environments and challenges all trigger neuroplasticity and neurogenesis that make you grow new brain cells and create new synaptic connections.

The Price of Longevity:

• Guppies who live in nature grow and reproduce faster because of predatory pressures than guppies without natural predators. When predators are removed, these same guppies will still go and have more offspring and live longer.
• Fruit fly mutants that live longer have even more progeny than normal
• Removing germline precursors in C. Elegans extends their lifespan. This is not due to sterility but because of hormonal signaling of the DAF-16/FOXO pathway that localizes DAF-16 in the adipose tissue.
• Humans can also suffer hormonal downregulation and low thyroid functioning with excessive caloric restriction and chronic stress.

There’s also the idea that stimulating growth with mTOR and IGF-1 will accelerate aging because of the growth mechanisms. However, there are as many reasons to think that inadequate levels of these pathways are as detrimental for longevity.

• mTOR helps to build muscle and prevents muscle wasting, which is increasingly more important as you get older.
• IGF-1 and mTOR increase bone density and joint strength, especially in cartilage and tendons.
• Both high and low levels of IGF-1 are associated with increased mortality in a U-shape curve trend.
• IGF-1 fights autoimmune disorders by increasing T-cells and supports proper growth.
• IGF-1 improves blood sugar regulation. Lower IGF-1 is associated with metabolic syndrome and insulin resistance. This may be partly due to low insulin sensitivity that can be improved by building more muscle and stimulating mTOR.

Blue Zones

There are 5 Blue Zones: Okinawa in Japan, Sardinia in Italy, Nicoya in Costa Rica, Icaria in Greece, and the Seventh-Day Adventists in Loma Linda (California).

There are about 6 characteristics shared amongst these people that help them to live longer:

1. They eat a wholefoods-based diet with a variety of vegetables, fruit, fish, some meat, tubers, legumes, and whole grains.
2. They engage in moderate physical activity most of the day by working, gardening, spending time in nature, and walking.
3. They have lower levels of stress and less work which decreases their cortisol and slows down telomere shortening.
4. They stick to the circadian rhythms by following day and night cycles, getting a lot of exposure to natural sunlight, sleeping well at night, and having several naps throughout the day.
5. They have a strong sense of community as all of the people are actively engaged with their families and others around them.
6. They eat moderately and never too much because eating more would mean they’d have to work longer.

These people eat meat but they also eat vegetables. They eat bread but they also eat fish. They eat dairy but they also eat fruit. This creates a more robust intestinal flora, which supports the immune system and prevents disease.

These people move around at a low to moderate pace most of the day by walking around the household, riding a bike to check up on the neighbors, doing gardening to grow their own food, hiking in nature, throwing hay or whatever the situation demands.

Enter TOR

Mechanistic Target of Rapamycin or Mammalian Target of Rapamycin or mTOR is a protein kinase fuel sensor that monitors the energy status of your cells. There are two mTOR complexes – mTORC1 and mTORC2. They stimulate cell growth, proliferation, DNA repair, protein synthesis, new blood vessel formation (angiogenesis), muscle building, the immune system and everything related to anabolism.

• mTORC1 functions as a nutrient sensor that controls protein synthesis. mTORC1 is regulated by insulin, growth factors, amino acids, mechanical stimuli, oxidative stress, oxygen levels, the presence of energy molecules (ATP), phosphatidic acid, and glucose. It’s a key factor in skeletal muscle protein synthesis.
• mTORC2 regulates the actin cytoskeleton, which is a network of long chains of proteins in the cytoplasm of eukaryotic cells. It also phosphorylates IGF-1 receptor activity through the activity of the amino acid tyrosine protein kinase.

Here’s a simple explanation of the mTOR pathway and how it works:

• Whenever your body detects excess energy in the system, it’ll try to direct it into the right places.
• The mTOR complexes are activated by growth factors, primarily insulin and IGF-1, but also nutrient factors like amino acids and protein.
• Insulin Receptor (IR) and IGF-1 Receptor (IGF-1R) are in the class of tyrosine kinase receptors. Tyrosine is an amino acid. Activating these receptors leads to the phosphorylation of insulin substrate receptor proteins (IRS).
• IRS activates a protein called phosphatidylinositol-3-kinase (PI3K) which further phosphorylates inositol phospholipids like PIP3. PIP3 interacts with proteins PDK1 and Akt.
• Akt is thought to be one of the main upstream regulators of mTOR. Akt is a family of proteins that comprise of Akt1, Akt2, and Akt3. Akt1-2 are expressed in skeletal muscle while Akt3 is not.
• Akt inhibits protein breakdown by regulating FoxO proteins. FoxO proteins regulate protein breakdown and autophagy-related pathways. They are inhibited by Akt, which prevents cell death.
• When there are plenty of nutrients around, mTORC1 binds to ULK1, which is an autophagy activating kinase and inhibits the formation of autophagosomes which would initiate autophagy. When energy gets depleted, mTORC1 becomes inactive and releases itself from the ULK1 complex, thus freeing up the formation of autophagosomes.

What Activates mTOR?

mTOR regulation is mostly mediated through AMP-activated kinase (AMPK). AMPK monitors the energy status of the cells through their glycogen content and ATP to AMP to ADP ratios. It’s called the adenylate energy charge that measures the energy status of cells.

In an abundance of ATP, the body has more resources to conduct repair and growth. If ATP levels are low or depleted, ADP and AMP ratios increase and they’ll get converted into ATP to maintain homeostasis. A reduction in energy activates AMPK which promotes catabolic pathways for maintaining energy homeostasis. AMPK inhibits muscle growth by suppressing mTORC1.

Here are the other mTOR activating nutrients and factors:

• Amino acids promote mTORC1 activity without affecting mTORC2 activity. Leucine specifically activates mTORC1 the most. Some evidence also hints that leucine’s by-product HMB may have a similar anabolic effect through the signaling pathway of mTORC1. Although, I’d say you’d get the same effect directly from leucine.
• Mechanical stimuli from resistance exercise, especially eccentric contractions, increases the levels of mTORC1. That’s why cold exposure can sometimes also activate mTOR in muscles – you freeze up and contract the muscles. Phosphatidic acid gets regulated by exercise which activates mTORC1.
• Phosphatidic acid enhances mTOR signaling and resistance exercise-induced hypertrophy. It’s found in cabbage leaves, radish leaves, and herbs or can be taken as a supplement.
• Ursolic acid stimulates mTORC1 after resistance training in mice. It stimulates anabolism via PI3K/Akt pathways. Ursolic acid can be taken as a supplement or found in foods like apples, bilberries, rosemary, lavender, thyme, oregano and many more.
• Creatine may potentially promote mTORC1 by increasing IGF-1 activity after exercise but doesn’t further potentiate mTORC1 several hours after exercise. So, the best time to take it is with your post-workout meal. It’s one of the most well-studied supplements that actually seems to work. 
• Testosterone and androgens can also signal mTOR and induce muscle hypertrophy. Testosterone has many anti-catabolic as well as anabolic properties, which is why high cortisol tends to wreak havoc on this hormone.

Suppressing mTOR with diet or certain supplements like Metformin and Rapamycin are common ways of treating cancer and tumor growth.

• Rapamycin inhibits mTORC1, which is thought to increase life expectancy in animal studies.
• Disrupting mTORC2 with rapamycin may induce insulin resistance as well as symptoms of diabetes and glucose intolerance.
• Increased glycolysis, which is the metabolism of glucose into lactate, is often found to be higher in cancer cells, also known as the Warburg Effect.
• Akt regulates Hexokinase 2, which is thought to cause this enhanced glycolysis in cancer cells. mTOR promotes the activation of insulin receptors and IGF-1 receptors, which is in most cases accompanied by glucose and glycolysis. Hence the association of mTOR with cancer.
• Patients with Alzheimer’s disease also show dysregulated mTOR activity in the brain and connection with beta-amyloid proteins.
• Methionine restriction could be beneficial for longevity as well. SAM (SAdenosyl- Methionine) is the 2nd most common cofactor in enzymes after ATP, which detects the presence of methionine-related nutrients in the body. One of the methionine sensors SAMTOR (S-adenosylmethionine upstream of mTORC1) inhibits mTORC1 signaling. Methionine restriction lowers SAM and increases SAMTOR, which improves glucose homeostasis and can promote longevity along the lines of caloric restriction. One of the reasons why it’s thought that restricting calories and methionine extends life is because of decreased mTOR and insulin.
• mTOR may promote intestinal inflammation as well as skin acne, which is more proof to how high mTOR all the time accelerates aging. However, this effect is probably due to a poor microbiome and other inflammatory lifestyle factors not necessarily mTOR itself. mTOR simply makes things worse in some cases because of its anabolic effects.

What Inhibits mTOR?

• Dietary protein restriction lowers mTOR. Amino acid deficiency, in particular, regulates mTOR.
• Calorie restriction lowers mTOR and promotes autophagy.
• Ghrelin the hunger hormone activates AMPK in the hypothalamus and inhibits mTOR.
• Fasting lowers glucose, insulin, and suppresses mTOR while raising AMPK. This is the most effective method of inhibiting mTOR. It also raises autophagy and promotes ketosis.
• Ketogenic Diets are moderate in protein and low glucose, which lowers mTOR activity. Glucagon, which is a hormone that raises in the presence of low glucose and insulin, activates AMPK and represses mTOR.
• Exercise inhibits mTORC1 in liver and fat cells. This is great because you’ll be preventing fat gain while promoting longevity and muscle growth. The post-exercise time window, however, facilitates muscle protein synthesis in muscle cells because of the mechano-overload. That’s another mechanism by which resistance training is great for increasing lifespan – more mTOR in muscles and less mTOR in fat cells.
• Glucocorticoids and cortisol get elevated during physiological stress. Cortisol helps to mobilize glycogen and fatty acids. This shifts the body into a more catabolic state.
• Metformin is a potent anti-diabetic drug that lowers blood sugar and insulin, thus lowering mTOR. Berberine is a medicinal compound that has similar effects.
• Rapamycin is an immunosuppressing drug that lowers mTOR. It’s been used to fight cancers and tumors in humans.
• Resveratrol is a compound found in certain fruit and red wine that has a longevity-boosting effect. Part of it has to do with sirtuins and autophagy.
• Curcumin inhibits mTOR signaling in cancer cells. Reishi fights tumors as well by blocking mTOR. Rhodiola Rosea and astragalus too.
• Anthocyanins found in blueberries and grape seed extract promote AMPK and block mTOR. Pomegranate as well.
• Alcohol activates AMPK and regulates the mTOR complex. It doesn’t go to say that drinking is going to boost your longevity. Remember that mTOR inhibition is just a single piece of the puzzle.
• Oleanolic acid contributes to anti-tumor activity. Main food sources of oleanolic acid are apples, pomegranates, bilberries, lemons, grapes, bilberries, and olives.
• Carnosine inhibits the proliferation of human gastric carcinoma cancer cells by retarding mTOR signaling. Carnosine is an amino acid with anti-aging and antioxidant benefits that fights free radicals as well. Interestingly, it’s found the most in animal foods and meat.

Benefits of mTOR

• mTOR is required for protein synthesis and skeletal muscle hypertrophy. Suppressing mTOR for too long or having too much autophagy leads to muscle atrophy and loss of lean tissue through sarcopenia, which can contribute to aging and metabolic disorders.
• mTORC2 regulates the distribution of mitochondria and mTORC2-activated AKT is linked to mitochondrial proliferation. mTOR also promotes mitochondrial biogenesis by activating PGC1-alpha.
  • mTORC2 localizes mitochondria-associated endoplasmic reticulum (ER) and mitochondria-associated membrane (MAM). This localization is stimulated by PI3K growth factors.
  • mTORC2 deficiency creates a defect in MAM, which causes an uptake of calcium in the mitochondria. Probably not good for atherosclerosis and plaque formation.
• mTOR can also help you lose weight and be healthier. mTORC2 regulates glucose homeostasis via Akt. Akt promotes glucose uptake by increasing GLUT4 translocation to the membrane in adipocytes. The same effect is also true because of increased muscle mass and insulin sensitivity that’s accompanied by muscle. If you have too low mTOR then you won’t be able to build muscle thus having poorer metabolic flexibility and predisposing yourself to disease.
• mTOR also contributes to neural plasticity and learning memory development. Neuroplasticity is a key factor in learning, skill acquisition, and memory retention. It seems that both too low levels of mTOR and overexpression of mTOR cause impaired learning and cognitive decline. Activating mTOR in prefrontal neurons by HMB inhibits age-related cognitive decline in animals. mTOR also helps to grow synaptic connections.

All in all, mTOR signaling seems to be more problematic in people who already have a certain disease such as cancer, tumors, diabetes, or Alzheimer’s.

You want to activate mTOR in muscle cells, brain cells, and mitochondria instead of fat cells and cancer cells.

• Exercise activates mTOR in the brain and promotes skeletal muscle mTOR. Resistance training, in particular, will make you build muscle through the mechanistic stimuli of mTOR.
• Time restricted eating is probably the most effective and most critical thing for controlling mTOR. Even though you may be eating a low mTOR diet you need autophagy as well if you want to promote life-span.
  • If you’re fasting for longer periods of time and you’re eating less often, then you need to make your meals more mTOR stimulating to counterbalance the catabolic effects of fasting and support muscle homeostasis.
  • If you’re fasting less and you’re eating frequently, then it’s indeed a better idea to keep your foods lower in mTOR as to avoid excess growth.
• The mTOR pathway has many functions beyond just muscle growth and anabolism. It regulates the immune system, fat storage, and with AMPK controls whole-body energy balance.

Is IGF-1 Good or Bad

Most of IGF-1 gets mediated by growth hormone that’s produced in the hypothalamus. When the anterior pituitary gland in the hypothalamus releases growth hormone into the blood, the liver responds by stimulating the production of IGF-1. IGF-1 activates the Akt pathway, which is a downstream activator of mTOR.

There are many functional benefits to IGF-1:

• IGF-1 supports muscle growth and protects against muscle wasting. It also promotes bone growth and strength. Protein and amino acids increase IGF-1 levels as well independent of caloric intake. 
• IGF-1 regulates glutathione peroxidase, which is one of the most potent antioxidant pathways in the human body. These antioxidant benefits can protect against heart disease by clearing out plaques in the arteries.
• IGF-1 fights autoimmune disorders by increasing T-cells and boosts the immune system.
• IGF-1 improves blood sugar regulation. Lower IGF-1 is associated with metabolic syndrome and insulin resistance

IGF-1 can protect cells against oxidative stress, which will prevent cell death and can protect against disease. However, if the person’s already sick and has cancer, then IGF-1 will also prevent cancer cells from dying in chemotherapy.

IGF-1 and Aging

• The association of IGF-1 and mortality follows a U-shaped curve with both too high and too low levels of IGF-1 are linked to increased mortality risk.
• IGF-1 is correlated with longer telomere length which is an important predictor of longevity. That’s why there’s this dichotomy between having enough IGF-1 for muscle and cellular maintenance VS not dying to the proliferation of cancerous tumors. Furthermore, IGF-1 has many benefits on cognition and brain functioning.
• When IGF-1 is low, inflammation tends to increase due to inadequate antioxidant and repair processes. IGF-1 stimulates collagen synthesis and prevents aging of the skin. However, too much IGF-1 and mTOR may cause acne and rashes.
• In healthy individuals, IGF-1 expression would be balanced by the IGF-1 binding protein (IGFBP), which blocks IGF-1s effects. That’s why IGF-1 is bad only if you have too much free serum IGF-1 in the blood. This may happen because the person is being more anabolic than their body needs to be whether due to sedentary living, eating too many calories, not doing proper resistance training, or some other metabolic mismatch.
• Elevating IGF-1 above a safe limit is also very difficult unless you’re taking growth hormone supplements, anabolic steroids, you have insulin resistance or you’re eating copious amounts of excess protein.

How to Inhibit IGF-1

• Caloric restriction and intermittent fasting can help to reduce cancer development, protect against cognitive decline, reverse diabetes and slow down aging.
• Intense walking affects serum IGF-1 and IGFBP3. This is probably because physical movement helps to lower insulin and blood glucose, thus lowering IGF-1 as well.
• Curcumin lowers IGF-1 by activating AMPK and autophagy.
• Luteolin inhibits proliferation of breast cancer cells induced by IGF-1. It’s a polyphenol and flavonoid that stimulates AMPK.
• EGCG from green tea inhibits IGF-1 stimulated lung cancer. Another polyphenol in action.

How to Increase IGF-1

• Deer antler spray extract is said to contain IGF-1 and promote the production of testosterone.
• Red meat, dairy products, and dietary calcium are associated with higher IGF-1.
• Dietary fat and carbohydrates raise IGF-1 and lower IGF-1 binding proteins.
• DHEA is an endogenous steroid hormone that supports muscle strength and IGF-1.
• Leucine and its by-product HMB supplementation increase growth hormone, muscle growth, and IGF-1.
• Low zinc causes low IGF-1 as it’s thought zinc potentiates IGF-1 actions.
• Selenium and magnesium are associated with total IGF-1.
• However, IGF-1 is poorly absorbed by the intestines because of being broken down very rapidly in the gut.
• Resistance training increases the bioavailability of IGF-1 and supports bone density, especially in older people.
• Sauna sessions can also boost growth hormone and thus increase IGF-1. In fact, growth hormone may rise by 140% immediately after a sauna session.

Should Old People Do Intermittent Fasting

The only problem with fasting when you’re older is that you may be more predisposed to muscle loss and catabolism. This may make you more prone to metabolic disease and more aging. As you lose muscle, you’re more predisposed to bone fractures, insulin resistance, neurodegeneration, and cardiovascular disease.

In general, the trend already shows that all the anabolic hormones like HGH and testosterone drop alongside with a reduction in lean body mass. Part of it has to do with becoming more sedentary and not doing resistance training but it’s also partly because of becoming less anabolic.

Leucine resistance, in particular, makes it more difficult for old people to maintain muscle, not to mention build it. That’s why longer periods of fasting may lead to accumulated sarcopenia. However, that can be easily alleviated by becoming more active and stronger.

To circumvent sarcopenia, you’d have to keep lifting weights, eat adequate amounts of protein, and avoid sedentarism. Increasing protein intake up to 35-40% can also be a good idea as to negate some of the leucine resistance. To stimulate MPS after exercise, you can even take 3-5 grams of leucine to promote muscle homeostasis.

It’s not recommended for old people above their 60s to have extended fasts for 3-5 days either. Going without eating for such a long time may have side-effects on muscle mass. The elderly go catabolic more easily because of low anabolic hormones. That’s why even on the daily IF schedule they should focus more on the 16/8-time frame instead of a very tight OMAD meal.

Principles of Metabolic Autophagy

• Time-Restricted Feeding as Long as You Can Every Day – This is probably the most cost-effective thing you can do to improve your health and longevity. By simply not eating and fasting instead is one of the easiest ways to promote longevity and health. There isn’t a real physiological reason to be eating any more than twice a day. Hell, most people will do perfectly fine with a single meal, unless they’re under some special requirements. Whatever the case is, the minimum for daily time-restricted feeding is the 16/8-hour window, even when trying to build muscle. Instead of eating for distraction, you should leverage the fasted state as long as you can and then eat to support your physical conditioning.
• Lift Heavy Things and Do Resistance Training – The goal of your exercise should be to promote muscle growth and maintenance. Having more lean tissue is one of the best things for healthy aging and longevity. That’s why you want to predominantly resistance training instead of cardio. At minimum, 2-3 and up to 4-6 times per week. If you’re working out more intensely more frequently, then you may have to adjust your fasting window to make sure you’re not getting weaker or losing muscle. Some days should still be kept for cardiovascular training and full-on recovery but they aren’t the main focus.
• Get a Sweat on Daily – It’s incredibly important to keep your lymph system flowing and more active. Modern life is already quite sedentary and that can cause stagnation within the body. A lot of digestion issues and toxicities occur because of not clearing out the lymph fluids. Exercising and moving around are one of the best lymph node stimulators but any form of sweating whether by going to a sauna, doing yoga or running is great.
• Maximize Nutrient Density – This means eating high-quality foods that have an abundance of micronutrients, minerals, and other cofactors. Your purpose isn’t to eat as many calories as you can get away with but to get more nutrition out of fewer calories. Mild caloric restriction and eating around maintenance is beneficial for longevity. Eat nose to tail, get adequate electrolytes, cover your essential nutrients, supplement your deficiencies, incorporate some superfoods into your diet, and cycle between different food groups. You shouldn’t deprive yourself of nutrients either. Doing intermittent fasting doesn’t mean you’re starving yourself. Quite the opposite. You’ll be getting more than enough nutrition. Just in a time-restricted manner.
• Eat Whole Foods (A Lot of Plants) – In terms of nutrient density, you’d have to focus on eating a lot of vegetables that have many vitamins and other beneficial compounds but not a lot of calories. Animal foods have their place but you shouldn’t overconsume them. Most of what you eat in terms of volume should still be plant-based. Meat, eggs, fish, and fats simply have more calories. The antioxidants and polyphenols from cruciferous, veggies, berries, and other plants are pro-longevity because of being nTOR as well.
• Control Blood Sugar and Insulin – This is one of the best ways to ensure stable energy levels, avoid health problems, and maintain a more effective state of nutrient partitioning. It’s just not a good idea to have high levels of blood sugar or insulin all the time and the research supports that. Instead, your goal should be to keep them relatively low the vast majority of time and only raise them where the body is more sensitive.
• Don’t Combine High Carb High Fat Foods – Avoid processed inflammatory foods that are low protein, high carb, and high fat because it’s a recipe for insulin resistance, diabetes, and over-eating. This change will drastically enable you to avoid most metabolic disorders. The short dopamine rush may feel good but it’s not optimal in the long run. You can apply the 80/20 rule but do it at your own responsibility.
• Limit Evolutionary Trade-Offs – Avoid the “natural diet” fallacy both in the context of eating too much protein and animal fat as well as the plant-based approach. It’s not a wise idea to go into the extremes and think that you’re somehow immune to all diseases. Who knows how your body individually will react to different foods. Maybe you’re not as insulin sensitive as you think you are to justify that carb-up. Likewise, don’t roll the dice with eating things that will potentially yield negative results but come with zero benefits. I’m talking about lectins, fruit, dairy, grains, vegetable oils, too much saturated fat, and carcinogenic meat…
• Stimulate mTOR and Anabolism Only When It’s Useful – You don’t want to be spiking insulin or mTOR just for nothing. To avoid any trade-offs in longevity, you want to eat ModTOR foods only after resistance training to support muscle homeostasis. At other times it’s better to stick to nTOR and autophagy-like compounds. This is relevant mostly when you’re eating more than twice a day. In the case of 2 meals a day, you’d want to make the first meal very low in anabolism and smaller in calories. The second one should be post-workout wherein you’re more sensitive to mTOR and insulin. If you’re not working out, then you’d be better off by limiting your protein intake and focusing on autophagy. You also don’t want to be eating a lot of meat, eggs, and fish every day. Most of your food should still be plant-based because of their nTOR qualities and polyphenols. Eat meat only after heavier resistance training workouts and not in excess. This way you’ll stimulate mTOR and anabolism only when it’s useful and without consequences on longevity.
• Cycle Between Anabolism and Catabolism – Don’t stay in either state for too long. If you’re anabolic too long, you may accelerate aging. If you’re catabolic too long, you may lose your muscle. Both aren’t optimal for longevity nor performance. That’s why you’d want to cycle between periods of being at a small surplus with staying around your maintenance and even dropping into a deficit. The human body evolved under constant energy stress and it’s what we thrive under. Never be stagnant or dysfunctional.
• Expose Yourself to Hormetic Stressors – Nutrition and exercise aren’t the only components of longevity. You also want to trigger hormetic adaptation outside of the gym. To live a longer and healthier life you have to become more resilient against stress and adaptable to the ever-changing conditions of the natural environment. Of course, modern life allows us to maintain homeostasis in everything we do whether that be our core temperature, daily routines, food consumption, or physical challenges but they’re elusive. To not be swept away by some unexpected circumstances, you want to follow a lifestyle that involves voluntary hormesis. Take cold showers, swim in icy lakes, turn off the central heating, burn some fat at the sauna, practice stress management, fast for 5 days a few times per year, and do something tough.