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AGE meeting June 1-4, 2007 San Antonio, TX
The American Aging Association (AGE) was founded by Dr. Denham Harman, who proposed the free radical theory of aging. AGE is the pre-eminent association of physicians and researchers devoted to understanding how aging occurs and how to reduce the painful effects often encountered as people age. I have been a member since 1990. Of the meetings I attend, AGE provides the most useful information on ways that I can age gracefully and research that holds promise to sustain my optimism. I have edited 25 pages of my notes down to this brief 4-page summary.
I. Can lifespan be substantially extended in humans? I spoke with Aubrey de Grey, famous for claiming he is likely to live to be 1,000 years old. Articles appeared recently in AARP magazine and last year in the Chronicle of Higher Education. A bet was placed in Science magazine a year ago. A scientist wrote "I offer $10,000 to anyone who can show Aubrey's ambition is ridiculous." In a year, only two people took the offer Science appointed an independent panel of gerontologists, and both entries lost. It is still realistic to plan to be 1,000 years old! (It is now possible to produce a fruit fly that has 10 times the life span of a normal fly, just by giving it a gene to prevent oxidative stress.)
We also discussed caloric restriction, a method of severe dieting that has been shown to extend lifespan. Aubrey extrapolated that it would not be useful to humans, based on this data:
He proposed that the caloric restriction process is probably based on the relative lengths of lifespan as compared to food scarcity. A short lived species will need caloric restriction life extension to survive food scarcity, while a long lived creature will not.
II. Blueberries and strawberries for a healthy brain - Biggest news of the conference - Eat blueberries and strawberries, preferably twice-a-day. Blueberries contain nutrients called ellagitannins and proanthocyanidins. Strawberries have cattagins. Both berries contains anthrocyanins. Each berry acts on a different area of the hippocampus and showed distinct effects in the brain, memory, and motor function. Eating both berries is likely to preserve and even improve memory. The ideal action can be obtained when they are eaten every 12 hrs. IF YOU WANT TO PRESERVE AND EVEN IMPROVE YOUR MEMORY AS YOU AGE, GET BLUEBERRIES AND STRAWBERRIES (AND FISH OIL).
In one study ongoing since 1999, people have been taking blueberry extract. They have been reported to increase hippocampal neurogenesis and plasticity, reduce Alzheimer's like changes, and decrease tumorigenesis. . In this study of people median age 70 for 5 years, errors in memory decreased by 9.5% on average based on a word recall test.
In animals, blueberries improve learning and maze performance and increase longevity.
In contrast, calcium overload causes neuronal damage, but enzyme CoQ10 therapy has beneficial effects. So there is reason for great concern about taking supplemental calcium and drinking milk. All the calcium people need is 800 mg per day, according to Prof. Walter Willett, Chair of Nutrition and Public Health at Harvard. For osteoporosis, it is most important to get exercise and 1-2,000 IU of vitamin D daily.
III. EXERCISE IS SO IMPORTANT
1. Hypoxia is good - Hypoxia is a shortage of oxygen. Hypoxia produces over 100 downstream gene products important in vascular remodeling, neuroprotection, glucose metabolism, angiogenesis, dopamine metabolism, cell growth and survival, and iron metabolism. Note exercise helps provide short-term hypoxia and thus is very good for health.
2. Temperature change is good - Repeated temperature fluctuation extends the lifespan of C. elegans. C. elegans lived twice as long when temperature was varied throughout their lives. Perhaps exercise helps people vary their body temperature, by raising our core body temperature during vigorous exercise.
3. Exercise helps your brain - One study looked at a fat diet and exercise in middle aged rats. Exercise was important to maintaining good brain function, but a high fat diet did not impair memory.
IV. Signalling molecules
A major change in nutrition is the realization that nutrients are signaling molecules, not just food. Science is now showing the hormones our bodies produce and the nutrients we obtain from food have similar controls on our metabolism, providing parallel regulatory pathways for health.
These signalling molecules control how DNA is expressed to synthesize RNA and proteins.
nutrient -> sensor molecule -> signal -> transcription of DNA -> synthesis of regulatory component -> control of gene expression -> process to metabolize nutrient
Here are a number of particular signaling nutrients that were described:
1. Nicotinamide - One I especially noticed was nicotinamide, related to vitamin B3, niacin. Nicotinamide is a SIRT1 inhibitor, and is very bad for health. Most vitamins use niacin or nicotinic acid, and these are good and have the reverse effect of nicotinamide. But some energy and multivitamins and energy drinks contain nicotinamide, and this is hazardous to your health.
2. Stem cell nutrients - A rapidly growing body of literature now indicates that certain nutrients, vitamins, and flavonoids could have important roles in the proliferation of stem cells as well as maintaining continuous replacement of the stem cells required for healthy self-renewal of mature cells in the blood, brain, and other tissues.
3. EGCG, found in tea, is a powerful anti-aging agent, based on mitochondrial health in human fibroblasts.
4. melatonin, Resveratrol, acetyl-L-carnitine, and Metformin were testing. Only Resveratrol extended fly life.
5. Cranberry supplement helps prevent aging. There was a 9% increase in lifespan of fruit fly with cranberry extract.
6. Vitamin E and coenzyme Q10 improve memory and motor function in aged mice. Most benefit was vit E, but best in combination. Not CoQ10 alone!.
7. Milk may be hazardous with age. Short term galactose supplementation exacerbates age-dependent motor deficits. Dietary galactose causes age associated motor dysfunction. Milk sugar is lactose, which is half galacatose.
8. Phosphate is bad for health. Soft drinks are packed with phosphate. Phosphate restriction alleviates aging in mice. So phosphate accelerates aging.
9. Growth hormone - When stimulated artificially, Growth Hormone is harmful. Deficiency prevents many tumors and reduces kidney troubles; excess causes cerebral hemorrhage; but the right amount maintains cognitive function.
V. Theoretical framework for the aging process - The acronym for lifespan one speaker described was LEGS. Longevity = Environment + Genes + Stochastic
In evolutionary terms, men have invested in genetics by fathering offspring, women have invested in the environment by helping offspring survive. Age is 80% environment; 20% genes - I was interested to see one advantage of being short - small guys live longer than big guys. High levels of growth hormone make you taller, but kill you eventually. Generally premature death in adults has strong genetic component, especially due to inflammation. Once again, vitamins C and E may be highly protective.
Here are mechanisms by which these things might happen:
A. Energy control - The aging process may be based on our ability to control our energy metabolism in response to the availability of food. Exercise, occasional stress and periodic hunger help maintain that control, while constant stress decreases our ability, as diagrammed below:
Exercise, Caloric Restriction, Stress
Energy abundant metabolism <-----------> Energy deprived metabolism
arrow is signaling pathways that are blocked by aging
B. Membrane pacemaker theory of aging - Creatures whose cell membranes resist oxidation most effectively are the longest lived - naked mole rat, echidna, human. So maintaining healthy cell membranes is important. Getting those unsaturated fatty acids in the diet, especially fish oil/omega-3, may be very important to prevent age-associated disease. In constrast, omega-6 fats, abundant in a meat based diet, are very hazardous. Omega-6 fats promote inflammation which blocks proper signaling.
C. Pathways to aging. These are specific independent causes of aging.
1. The insulin regulation pathway, IGF-1, is very important. IGF kills mitochondria, and it causes increased oxidative stress. Whenever you turn on insulin receptors, by eating starch and sugar in high glycemic index foods, you are turning on those receptors and accelerating death. Whereas eating whole grain foods and healthy meals is fine.
2. The effectiveness of the Electron Transport Chain for energy production in the mitochondrion is a second vulnerable piece of our metabolism. This pathway mainly needs good nutrition: vitamins C and E, polyphenols from fruits and vegetables, fish oil for membranes, N-acetyl carnitine and lipoic acid for fat metabolism.
3. The Dietary restriction pathway is now recognized to control a set of signals and genes that allow our bodies to cope with stress. This pathway is not just affected by hunger, but by other stresses, like exercise. The correct amount is good for health, too much or too little is hazardous. For exercise, you want 30 to 90 minutes per day!
VI. Odds and ends - a few notes on random things of interest.
1. Telomeres may not be the answer. Telomere length in the healthy oldest old humans is not exceptional. Comparing 156 health seniors over 85 with 46 healthy younger controls found no significant difference in telomere length in WBCs
2. Corticosteroids and exogenous cortisol accelerate human aging and induce harmful stress pathways. So be cautious when the doctor prescribes corticosteroids to treat medical conditions, which they often do.
3. DHEA and serum antioxidant status were correlated in 197 healthy adults, and both decreased with age. DHEA and antioxidants may have roles regulating each other. It is possible that maintaining high antioxidant levels through vitamins may improve DHEA levels safely.
VII. A CHART OF THE DETAILS OF HOW WE AGE METABOLICALLY - Here is an enormous on line poster that shows all of the details known about what happens metabolically to cause aging. http://www.legendarypharma.com/chartbg.html