Prolonging Healthy Aging: Longevity Vitamins and Proteins

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Prolonging Healthy Aging: Longevity Vitamins and Proteins Proceedings of the National Academy of Science (PNAS) October 23, 2018; Vol. 115; No. 43; pp. 10836–10844

Bruce N. Ames: From the Nutrition and Metabolism Center, Children’s Hospital Oakland Research Institute, CA. This study cites 148 references.

A recent (May 1, 2020) PubMed literature search using “Ames BN” locates 400 articles.

V/M = Vitamins and minerals


1) Proteins/enzymes are classified into two classes according to their essentiality for immediate survival/reproduction and their function in long-term health:

Survival proteins


Longevity proteins

2) The Triage Theory:

• “A modest deficiency of one of the nutrients/cofactors triggers a built-in rationing mechanism that favors the proteins needed for immediate survival and reproduction (survival proteins) while sacrificing those needed to protect against future damage (longevity proteins).”

• Many nutrients “play a dual role for both survival and longevity.”

3) “Impairment of the function of longevity proteins results in an insidious acceleration of the risk of diseases associated with aging.”

• “Nutrients required for the function of longevity proteins constitute a class of vitamins that are here named ‘longevity vitamins’.”

• Taurine [details below] should be considered as a conditional vitamin.

• These 10 compounds should be considered as putative longevity vitamins:

•• The fungal antioxidant ergothioneine

•• The bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine

•• The plant antioxidant carotenoids lutein, zeaxanthin, lycopene, α- and β-carotene, β-cryptoxanthin

•• The marine carotenoid astaxanthin

4) “Because nutrient deficiencies are highly prevalent in the United States (and elsewhere), appropriate supplementation and/or an improved diet could reduce much of the consequent risk of chronic disease and premature aging.” [Key Point]

5) Dr. Ames proposes that an “optimal level of many of the known 30 vitamins and essential minerals/elements (V/M), plus that of 10 new putative vitamins described herein, is necessary for promoting healthy aging.” [Important]

6) The “triage theory” states that when there is a V/M shortage, the proteins/enzymes that are sacrificed are the ones necessary for supporting longterm health. [Important]

• Many V/M are necessary for supporting long-term health.

• Many V/M deficiencies “increase the risk of future disease and shortens the lifespan.”

•• These V/M are “longevity vitamins,” and the proteins associated with them are “longevity proteins.”

7) “Approximately 30 V/M are cofactors necessary for metabolism to function properly and were discovered because severe dietary deficiencies were linked to serious adverse health effects.”

• Vitamins A, B1, B2, B6, B12, biotin, C, choline, D, E, folic acid, K, niacin, pantothenate; and minerals/elements calcium, chloride, chromium, cobalt, copper, iodine, iron, manganese, magnesium, molybdenum, phosphorus, potassium, selenium, sodium, sulfur, and zinc.

• The marine omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentanoic acid (EPA) are also essential but they are not vitamins.

• Nine essential dietary amino acids are also important for the synthesis of proteins and hormones.

8) Most of the world’s population, including developed countries, consume many of the V/M below recommended levels.

9) The estimated average requirement (EAR) values are the intake level for a nutrient at which the needs of half of the healthy population is adequate and half is inadequate. The United States population ingesting V/M quantities below the EAR (including fortifications and supplements) are:

• Vitamin D 70%

• Vitamin E 60%

• Magnesium 45%

• Calcium 38%

• Vitamin K 35%

• Vitamin A 34%

• Vitamin C 25%

• Zinc 8%

• Vitamin B6 8%

• Folate 8%

• “Intakes of the marine omega-3 fatty acids DHA and EPA are also remarkably low in the United States population.”

10) “A diet containing much of its calories as refined foods and sugar is deficient in V/M and leads to an unhealthy and shorter life.” [Key Point]

11) The triage theory notes, “modest V/M deficiencies—insufficient to elicit overt symptoms of severe deficiency—might contribute significantly to the aging process and the diseases of aging.” [Key Point]

• “A strategic rationing response has been selected through evolution, which ensures that when a moderate shortage of a V/M is encountered, the scarce V/M is preferentially retained by those V/M-dependent proteins/enzymes that are essential for survival and reproduction, such as proteins essential for early development and immediate survival (survival proteins).”

• “Proteins/enzymes needed for maintaining long-term health by preventing insidious damage are starved for that V/M and become increasingly inactive, thus leading to an increase in diseases of aging.”

12) “A major aspect of degenerative aging is that the damage is insidious and clinically not obvious because it accumulates slowly over time and is apparent only later in life. The connection to V/M shortages is underappreciated.”


• Some vitamin K-dependent proteins are required for short-term survival (like blood-clotting).

• Other K-dependent proteins are involved in long-term health.

13) Adequate V/M throughout life plays an important role in healthy aging.

14) Longevity proteins are sacrificed to allow for survival during triage rationing, but they also protect against diseases of aging.

• Longevity V/M are needed for the function of longevity proteins, and a shortage of which results in damage that is cumulative and insidious.

15) Survival enzymes/proteins are needed for short-term survival and reproduction, and are preferentially supplied with a V/M necessary for their function.

• Survival V/M are needed for the function of short-term survival proteins.

16) V/M that support both survival and longevity proteins are subject to triage rationing favoring survival. [Key Point]

• Hence, their shortage leads continuously to accelerated aging. [Key Point]

17) There are some compounds that are needed only for longevity, and therefore are not essential for short-term survival. These compounds have not been recognized as V/M, but effectively function as longevity V/M (the 10 listed above).

18) Most V/M necessary for the proper function of longevity proteins/enzymes are also survival V/M. These include:

• Vitamin K

• Selenium

• Vitamin D

• Marine omega-3 fatty acids DHA and EPA

• Magnesium

• Taurine

•• “The levels of each of these are inadequate in a large percentage of the American population, and these deficiencies are a major contributor to unhealthy aging.”

19) “Vitamin D levels are inadequate in 70% of the United States population.”

• “Almost all dark-skinned people residing in northern latitudes are particularly deficient.”

• About 2,700 binding sites have been found in the human genome as interacting with the vitamin D receptor protein (14).

• Vitamin D deficiency causes or is associated with a large number of diseases that affect healthy aging, including all-cause mortality, cancer, cardiovascular disease, diabetes, and brain function.

• “It is particularly important to tune up metabolism with respect to vitamin D.”

• There is no increased risk of vitamin D toxicity even when blood levels of 25(OH)D were as high as 100 ng/mL.

• Vitamin D is “important for a healthy long life, and thus it is a longevity vitamin.”

20) The intake of DHA and EPA is inadequate in most of the US population.

• Low EPA and DHA levels in red blood cells is associated with increased allcause mortality.

• Each 1% increase in plasma DHA/EPA was linked with a 20% decreased risk in all-cause mortality. [Very Important]

• DHA/EPA are present in high levels in the central nervous system and are important for brain.

• Omega-3 fatty acids supplementation is a promising treatment for schizophrenia.

• Low blood levels of DHA/EPA are associated with a faster rate of telomere shortening, a marker of cell aging.

• DHA/EPA are important for vitamin D steroid hormone effectiveness.

• DHA/EPA are inefficiently made from linolenic acid [plant-based omega-3].

21) Magnesium (Mg) is present in the center of the chlorophyll molecule, with plants being a major dietary source.

• “Mg deficiency affects about 45% of the United States population and has been associated with increased all-cause mortality, poor DNA repair capacity, increased risk of lung cancer and various other kinds of cancer, heart disease, telomere shortening, and risk of stroke.”

• Mg deficiency is a principal driver of CVD, “a worldwide under-recognized problem, and thus that it is a major public health crisis.”

• Mg is required to convert vitamin D to its active steroid hormone form.

22) Conditional Vitamins are synthesized by the body, but not at a level that is sufficient to optimize metabolism.

23) Choline is a conditional vitamin

• Only 11% of women achieve the recommended intake of choline.

• Choline deficiency results in DNA strand breaks and affects brain development.

24) Taurine is also a conditional vitamin; it is synthesized in humans, but not in sufficient amounts. [Taurine is an organic compound that is widely found in animal tissues, especially in fish and meat. It can be synthesized from cysteine. It may be low or negligible in a strict vegetarian diet {important}.]

• Taurine is important in preventing numerous health problems, such as CVD, brain function, diabetes, and mitochondrial diseases.

• Taurine functions as both a survival vitamin and a longevity vitamin.

• Taurine is located in the cytosol and in mitochondria and it is present in virtually all human tissues at millimolar concentrations.

• Good dietary sources of taurine include fish and other seafood, seaweed, eggs, and dark-meat poultry.

• Taurine is particularly important in the mitochondria and deficiencies are associated with mitochondrial diseases.

• Taurine improves mitochondria energy production, reducing exercise-induced fatigue and improved recovery.

• Taurine is the main buffer against mitochondrial oxidant production.

• Taurine supplementation lowers blood pressure and improves vascular function. “Taurine consumption was the most significant factor associated with reduced risk of ischemic heart disease (IHD).”

•• “Japanese people in Okinawa had the highest taurine dietary intake and the lowest incidence of IHD and longest lifespan.”

• “Taurine plays an important role in brain development, including neuronal proliferation, stem cell proliferation, and differentiation.”

• Taurine has no toxic effects in humans.

• Taurine is a neuromodulator in the central nervous system.

• Taurine inhibits the N-methyl-D-aspartate receptor [NMDA]. [Important]

• In diabetics, taurine supplementation remediates retinopathy, neuropathy, nephropathy, cardiopathy, atherosclerosis, altered platelet aggregation, and endothelial dysfunction.

• Taurine is important for fetal development, and because the human fetus cannot synthesize taurine it must be provided by the mother.

• “Taurine is well established as an important conditional vitamin for survival functions and for healthy longevity.”

25) Dr. Ames believes that other conditional vitamins include lipoic acid, ubiquinone, and carnitine.

26) Dietary biochemicals that are not officially recognized as vitamins but have a positive age-delaying effect are called Putative Longevity Vitamins. They reduce the accumulation of long-term oxidative damage. They are not classified as “survival vitamins”:

• Ergothionine (ESH) A fungal antioxidant

• Pyrroloquinoline Quinone (PQQ) A bacterial compound pyrroloquinoline quinone (PQQ)

• Queuine A bacterial compound

• Carotenoids (seven plant compounds, one marine compound)

27) “Vitamin C is categorized as a survival vitamin because, in addition to being an antioxidant, it also functions as a co-factor for survival proteins.”

28) “Vitamin E is a fat-soluble, free-radical scavenger/chain-breaking antioxidant, and is not required for any known protein/enzyme functions.”

29) Ergothioneine (ESH)

• Synthesized by most mushrooms (highest in oyster and king boletus mushrooms, lowest in white-button commercial mushrooms), cyanobacteria, and many types of soil bacteria, but not by plants or animals.

• Also found in beef, pork, lamb, and chicken.

• Present in almost all human cell and tissue types and plays a significant role as an antioxidant.

• Levels decrease significantly with age, especially after past 80 years.

• Acts as an adaptive antioxidant for the protection of injured tissues.

30) Pyrroloquinoline Quinone (PQQ)

• “PQQ is made by many species of bacteria, but not by animals or plants.”

• PQQ is “synthesized by soil bacteria, enters plants from the soil, and thus enters human diets; it was detected in every sample of fruits and vegetables tested.”

• “PQQ is a powerful antioxidant and is much more stable than ascorbic acid.”

•• “In redox cycling, PQQ has 20,000 potential catalytic cycles, compared with 4 for ascorbic acid.”

• The health benefits of PQQ in humans include antioxidant activity, neuroprotection, cognition, and lowering the level of inflammatory C-reactive protein.

• PQQ improves mitochondrial efficiency and induces mitochondrial biogenesis.

• “PQQ is promising as a longevity vitamin in humans. It is necessary for mitochondrial health.”

31) Queuine

• Queuine is an evolutionarily ancient compound that is derived from bacteria.

• All eukaryotic organisms, including humans, convert queuine to queuosine.

• Queuine is required to convert:

•• Phenylalanine to tyrosine, tyrosine to DOPA, and DOPA to epinephrine and norepinephrine

•• Tryptophan to serotonin

•• Arginine to nitric oxide (NO)

32) Carotenoids

• There are ∼600 carotenoids synthesized by plants, but not by animals.

• They act as antioxidant pigments in all plants and usually contain 11 conjugated double bonds, which accounts for their yellow/orange/red colors.

• All photosynthetic plants synthesize carotenoids to quench singlet oxygen, a highly energetic and toxic form of oxygen created in cells by strong light.

• These six carotenoids account for 95% of the carotenoids found in the blood and brains of North Americans:

•• Lutein

•• Zeaxanthin

•• Lycopene

•• α- and β-carotene (a precursors of vitamin A)

•• β-cryptoxanthin (a precursors of vitamin A)

• A seventh carotenoid, the powerful marine carotenoid astaxanthin, contains 13 conjugated double bonds.

• “There is good evidence that these carotenoids help optimize a healthy lifespan.”

• “Carotenoids are included among putative longevity vitamins because of the evidence that they protect long-term health.”

33) “Prolonging good health while aging is an important issue in a world with large increases in life expectancy.”

34) “The relatively simple approach of securing sufficient intake of well-known dietary V/M, plus taurine, plus the 10 putative longevity vitamins introduced here, could lead to healthy aging by ‘tuning-up metabolism’ and promoting metabolic harmony and health.” [Key Point]

35) “By optimizing survival and longevity V/M intake throughout life, premature, insidious, and increased risk of degenerative diseases may in large part be preventable.” [Key Point]

36) “V/M deficiencies, as indicated by intakes below the EAR, are common in the United States and around the globe, especially among the poor, children, adolescents, the obese, and the elderly.”

37) “Evidence is accumulating that lack of foods that are particularly nutrient-rich is a contributor to diseases of aging.” [Important]

38) “Healthy foods are nutrient-dense, containing high levels of V/M, fiber, and longevity vitamins, relative to calories.”

• “Humans should be able to stay healthier longer during old age if nourished appropriately.”

39) “Some of the insidious damage due to a nutrient shortage may be reversible once the V/M intake is increased.” [Important]

40) “Obese individuals are particularly deficient in V/M, which is a likely explanation, among others, for a decrease in longevity through an increased frequency of every age-associated disease that has been examined, including cancer, heart disease, brain decay, and immune decay.”

• “The health and longevity of the obese would benefit greatly from an improvement in their V/M intake.”

41) “An important concept relative to the use of vitamins for health is the fact that over 50 human genetic diseases can be ameliorated by the administration of high doses of supplements.” [Important]

• “Supplementation raises the concentration of the needed coenzyme to levels that overcome a defect in the enzyme-binding site (which is likely to be deformed by mutation or aging-related membrane rigidity) besides possibly affecting the abundance and stability of some proteins.” [Key Point]

42) “Eventually, the age of preventive medicine will take into consideration the major effects of V/M components.”

43) “Two examples of consequences of V/M insufficiency, which are measurable, are increased DNA damage and mitochondrial decay.”

44) The benefits derived from an improved V/M utilization is:

• Prevention of the degenerative diseases of aging

• Lowering medical costs

• Increases savings

45) “In conclusion, in addition to keeping physically fit, the low hanging fruit in prolonging a healthy aging lies in optimizing V/M intake.” [Key Point]

Please read all precautions before consuming any supplement. Consult with your healthcare practitioner, if you have any concerns.

The following list with links correspond to the recommendations for longevity supplements described above. These are what I take, personally – Dr. Williamson


Multiple Vitamin-Mineral: Two Per Day Capsules

Super Omega-3 Plus EPA/DHA Fish Oil, Sesame Lignans, Olive Extract, Krill & Astaxanthin: 2 per day

Vitamin D3: 1 per day

Magnesium: 1-3 per day

Super K Elite: 1 per day

Super Ubiquinol CoQ10 with Enhanced Mitochondrial Support: 1 per day

Mitochondral Energy Optimizer with PQQ: 4 per day

Cognitex Elite Pregnenolone: 2 per day

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