Life Extension Magazine®

Issue: Sep 1999

Eat Less - But Do Eat Lots of Blueberries

Anti-aging therapies, caloric restriction, blueberries and genes were among the highlights of the joint AGE and American College of Clinical Gerontology conference.

By Ivy Greenwell

The 1999 joint conference of the American Aging Association (AGE) and the American College of Clinical Gerontology was widely regarded as particularly exciting. There was a feeling of optimism about the tremendous progress in our understanding of the aging process, and the emerging knowledge of how to slow it down.

We already have the knowledge of how to prevent or at least delay many age-related degenerative diseases that were once regarded as "normal aging." Soon we may have the means to effectively extend our life expectancy, and ultimately even the maximal life span of our species.

Caloric restriction promotes longevity

According to the current consensus, calorie restriction is the only reliable way to extend maximum life span (as opposed to average life span). Most of our free radical production comes from the energy-producing activities in the cell organelles known as mitochondria. As we age, the mitochondria become more and more damaged, producing less ATP (our energy molecule) and more superoxide radicals, which in turn further damage these tiny "energy furnaces." The rate of mitochondrial damage could be a key factor in determining the rate of aging. Calorie restriction translates into lower levels of free radical production in the mitochondria. But other physiological phenomena associated with calorie restriction are also likely to play a role in promoting longevity. Dr. Mark Lane of the National Institute on Aging in Baltimore presented a summary of the effects of calorie restriction.

Calorie restriction is known to reduce serum glucose and insulin levels. Both of these typically rise with age and age-related increased obesity. High glucose levels lead to the formation of harmful glycation products as glucose cross-links with body proteins such as collagen. Elevated insulin in turn has a number of harmful effects, including more production of inflammatory prostaglandins, which suppress the immune response, among many other negative consequences.

Dr. Lane stressed that there is a huge difference in baseline insulin levels between old calorie-restricted animals as compared to controls. The lowering of serum glucose and insulin is one of the earliest and most dramatic results of calorie restriction, and is perhaps the primary way in which calorie restriction works to extend life span.

It is intriguing that the famous daf-2 gene in the nematode C. elegans is related to insulin pathways. When daf-2 is altered to reduce its activity, the worms age more slowly.

Calorie restriction also produces an elevation in the levels of stress hormones known as glucocorticoids. It is a moderate stressor, mobilizing the body's defenses in a benign way. Thus, except for the stress of cold temperature, calorie-restricted animals have better stress tolerance, which contributes to longevity. Not surprisingly, they also have an attenuated inflammatory response to inflammatory agents, and are resistant to a variety of toxins. Researchers speculate that being exposed to mild stress (calorie restriction) upregulates defenses to major stress.

In addition, calorie-restricted animals show evidence both of lower production of free radicals in the mitochondria, and of better antioxidant defenses, as shown by increased catalase activity. Finally, there are changes in growth hormone secretion and insulin-like growth factor-1 (IGF-1) levels. While the growth hormone pulses are better preserved in calorie-restricted animals (which do not show the typical age-related rise in somatostatin), their serum IGF-1 levels are lower, which may give them increased resistance to tumors. When injections of IGF-1 are given to calorie-restricted animals, they lose their tumor resistance. It seems that growth factors and oxidative stress use the same pathway to activate cell proliferation.

Dr. William Sonntag of Wake Forest University stressed that serum IGF-1 levels are hardly the whole story. We have to look at tissue levels of free IGF-1 before we can truly conclude anything about the role of IGF-1 in calorie restriction. Such measurements are currently difficult to conduct. Dr. Sonntag also pointed out that aging calorie-restricted rodents maintain a high vascular supply to the brain and learning ability. In addition, they show better immune function, greater cellular protein synthesis, and better preservation of bone mass and skin thickness than controls.

Considering the controversy about growth hormone replacement, it needs to be stressed that only pharmacological levels of growth hormone are implicated in a shorter life span (as implied by shorter life spans of transgenic mice that produce abnormally high amounts of growth hormone). Growth hormone replacement at normal levels does not seem to affect life span.

An additional difference between calorie-restricted animals and controls is a decrease in long-chain polyunsaturated fatty acids and increased oleic acid (a monounsaturated fatty acid abundant in olive oil) in the tissues of calorie-restricted individuals. The result of this altered fatty-acid profile may be lower levels of proinflammatory prostaglandins, which are derived from arachidonic acid.

Finally, calorie-restricted monkeys do not show the steep decline in DHEA characteristic of aging primates. This raises the possibility that a less severe calorie restriction combined with DHEA supplementation might produce results comparable to those of more severe calorie restriction. Rick Weindruch, however, stated that supplementing rodents with DHEA in addition to standard calorie restriction did not produce benefits beyond those of calorie restriction.

Do we already have any human data relevant to the benefits of calorie restriction observed in rodents and rhesus monkeys? Perhaps the closest we have is a National Institute on Aging study of 900 non-diabetic human volunteers, which found that men with the lowest insulin levels seem to live the longest.

It is not only diabetics who show premature aging. The results of calorie restriction studies strongly imply that in order to preserve good health and slow down aging, one needs to maintain serum glucose and insulin levels within the low-normal range. Some of the scientists present at the conference were already practicing calorie restriction. The usual objection is that most people would be either unwilling or unable to lower their calorie intake. It is possible, however, that we could get around this problem with the use of "fake carbohydrates," such as are commonly found in products designed for diabetics, and/or the use of supplements that inhibit the absorption of glucose.

Do long-lived beings come in small packages?

A team from Southern Illinois University, headed by J. Mattison, presented intriguing findings on the longevity of Ames dwarf mice. These mice are infertile mutants that are only about one-third the size of their normal siblings and they live much longer.

The dwarf mice have lower blood glucose and lower body temperature than normal mice, but they eat the same amount of food (or more) per gram of body weight. In addition, they are not lean and can even become obese. Thus it must be concluded that their longevity is not related to voluntary calorie restriction. The authors are in the process of studying whether imposed calorie restriction can extend the already exceptional life span of dwarf mice even further.

The dwarf mice do not bear fewer tumors than normal mice, but their tumors have a later onset and appear to grow more slowly. It is also interesting that old dwarf mice do not show much "cognitive decline," as measured by performance on various learning tasks.

Do these findings apply to humans? It is usually pointed out that human dwarfs suffer from various deformities and pathologies. In a private communication, however, one of the authors of the study, Dr. A. Bartke of Southern Illinois University, revealed that during a recent endocrinology conference, a human geneticist from Emory University presented data on patients with mutations at the same locus as the Ames dwarf mice. It appears that this subcategory of human dwarfs (first described in the early 1900's as the "little people of Krk") do live a very long time.

As Dr. Bartke states, "there seems to be something about being small that predicts longer life. It may be small size per se, perhaps some size-related 'efficiency,' less load on the heart or something of this sort. Or the size is a marker for something else that is very important, for example the amount of food and energy metabolism-oxidative radicals? Insulin?-it takes to reach certain adult size and to maintain a body of this size. Smaller people also may have reduced risk for cancer, which could be what makes them live longer, or it could be a sign that they age more slowly."

Preventing premature aging

A very interesting and somewhat offbeat lecture pertained to the life span of dogs. Michael Hayek of the Iams Company pointed out that indeed small dogs live longer. Smaller dogs such as Fox Terriers can live up to 19 years, whereas Great Danes tend to die when they are five or six years old. Irish Wolfhounds are likewise short-lived. The cells from larger dogs have been found to undergo fewer cell divisions than cells from small dogs. The cells from small dogs can replicate for a longer time, showing more resistance to cellular senescence.

It has also been found that Fox Terriers (chosen as the model of a smaller dog) have superior lymphocyte proliferation, giving them an immune advantage.

When the physiological changes associated with canine aging are examined, three primary factors emerge: elevated glucose and insulin levels, increasing immune dysfunction, and an increase in the pathological intestinal flora. Luckily for dog owners who wish their pets to live as long as possible, these three factors can be easily counteracted.

In older dogs, just as in older humans, we see slow glucose clearance and much greater rise in insulin after a meal. It has been found that the chief problem is the inclusion of rice in dog food. Rice causes higher blood sugar and elevated insulin, with consequent increase in body fat (interestingly, this does not happen in young animals). Fortunately, dogs seem to respond well to the exclusion of rice and inclusion of fiber. Fiber is beneficial for the intestinal flora. In addition, dog food can be made to include nutrients especially designed to promote healthy intestinal bacteria. Dog food should also include antioxidants such as vitamin E and beta-carotene in order to promote immune health.

Thus, it is relatively easy to improve the health of dogs by simply improving the nutritional quality of dog food. The same easy measures-the exclusion of high-glycemic carbohydrates and addition of antioxidants and fiber-appear to have enormous anti-aging implications for humans as well. It is ironic that pet food is engineered according to research findings, while millions of children are being raised on junk food, and the elderly tend to eat a notoriously poor diet.

Ways to slow down brain aging

Lipoic acid was also discussed as an important means to slow down brain aging. Brain diseases are the eighth leading cause of death. Part of the pathology that is seen in cerebral aging is an increase in the levels of iron, together with a parallel decrease in tissue ascorbate. This leads to increased levels of free radicals in the brain tissue, and neural dysfunction and death. The study by Jung Suh and colleagues at the Linus Pauling Institute found a significant reversal of this pattern in rats receiving 4mg/day of lipoic acid. Lipoic acid produced a 60% reduction in the total tissue iron in the forebrain, and a "substantial" increase in forebrain ascorbate (vitamin C) levels. Other brain regions did not appear responsive to lipoic acid. This suggests that the forebrain, a region involved in cognition, has a special facility for the uptake and metabolism of lipoic acid. Lipoic acid's neuroprotective properties most likely comprise its ability to chelate free iron, in addition to its antioxidant effects, and the ability to regenerate ascorbate.

Other lectures and poster presentations also suggested that lipoic acid reduces oxidative stress in the mitochondria of the heart muscle, and raises the levels of ascorbate and glutathione in the heart and liver mitochondria. The restoration of ascorbate levels was particularly striking: supplemental lipoic acid was able to restore cardiac ascorbate levels in old rats to those found in young rats.

Since lipoic acid functions as a mitochondrial coenzyme essential for the oxidation of the alpha-keto acids in the energy-producing Krebs cycle, its importance for efficient energy production by the mitochondria seems obvious. It is probably by increasing mitochondrial energy output that lipoic acid is able to lower blood glucose levels and the formation of harmful glycation products. Lipoic acid is thus emerging as an extremely important anti-aging agent.

(Parenthetically, there was also a lecture on the decrease of glycation products with the use of a "glyconutritional." The speaker would reveal only that the product contains a substantial amount of mannose and fucose.)

Deprenyl (selegiline) and its new close analog rasagiline are of great interest because they not only slow down aging, but may produce life span extension. Both deprenyl and rasagiline selectively increase the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase, especially in dopamine-producing regions of the brain. The lecture given by Dr. Kitani revealed that rasagiline (and thus probably also deprenyl) also increases SOD and catalase activity in the heart and the kidneys. Interestingly, the lower dose was more effective than the higher dose. Rasagiline does not seem to offer any advantages over deprenyl, a drug used by some anti-aging researchers. Dosage is obviously crucial.

Still other ways to protect the aging brain were mentioned, such as anti-inflammatories (let us hope that the new COX-2 inhibitors such as Celebrex and Vioxx will prove much safer than nonselective NSAIDs such as ibuprofen and aspirin). Since inflammation-related damage to the brain starts to show up already in midlife, one should not wait until old age to begin a preventive anti-inflammatory treatment.

Estrogen replacement in postmenopausal women has also been shown to help prevent Alzheimer's disease. In fact, like many other phenolic compounds, estrogens are potent antioxidants. A sufficient dose of estrogen can totally prevent lipid peroxidation in brain cell membranes. However, like most antioxidants, estrogens need to be recycled back to their antioxidant state, or else they can act as pro-oxidants. Here glutathione appears to play a critical role. Hence a woman taking estrogen replacement should be aware of the need to keep her glutathione levels as high as possible. This can be accomplished by taking lipoic acid, N-acetyl-cysteine (NAC), and anthocyanins such as those contained in blueberries and bilberries.

Besides their antioxidant effects, estrogens also increase the release of acetylcholine, activate various methylating enzymes, act to prevent the formation of the amyloid plaque, decrease the production of pro-inflammatory cytokines, and much more. The benefits of estrogen replacement for brain health are beyond question: the higher the dose and the longer the duration of supplementation, the greater the protection against dementia. The point is to supplement estrogen in a safe way. Taking glutathione-raising supplements is a very important step toward making estrogen replacement safer.

It is possible that men can obtain similar neuroprotective benefits from testosterone replacement, since the male brain converts a significant portion of testosterone into estradiol. In fact, older men have higher estradiol levels than women of the same age who are not taking hormones. This has been cited as one factor that may explain the dramatic female prevalence of Alzheimer's disease. Since 40% of women over 80 (and over 50% of women over 90) suffer from this terrible disorder, at an enormous cost to society, spreading information about the many ways to prevent it or at least delay Alzheimer's disease is of enormous importance.

Antioxidants such as vitamins C and E have been documented to protect the brain. However, it turns out that the bioflavonoid called quercetin, present in onions, apples, and especially in ginkgo biloba, is particularly effective, as are anthocyanins (bilberry extract and blueberries are a rich source of anthocyanins). Anthocyanins have been found to be more protective against free radical damage induced by the beta-amyloid protein than vitamins C and E. As Dr. Bruce Ames of Berkeley pointed out, gamma tocopherol is needed for scavenging nitrogen free radicals, such as the dangerous peroxinitrite radical.

Speaking of nitrogen, a new class of synthetic antioxidants called nitrones is also showing great promise. Nitrones react with free radicals to form nitroxides, which are further converted to harmless compounds. Besides acting as antioxidants, nitrones also have a significant anti-inflammatory effect. In animal studies, they have been shown to help prevent cognitive dysfunction and extend longevity.

Using a variety of antioxidants seems more effective in protecting the brain than relying on any single antioxidant.

Finally, heat shock proteins also appear to prevent damage to the neurons. After a discussion of various ways to protect the brain against aging, including calorie restriction and neuroprotective agents, one conference participant asked, "Wouldn't it be cheaper to just give the animals a sauna every day or every other day?" Indeed it would. It was quickly pointed out, however, that calorie restriction, a particularly effective way of slowing down brain aging, also provides a multitude of benefits that are difficult to replicate in any other way. Nevertheless, regular sauna remains a very promising and much underutilized anti-aging treatment.

Osteoporosis does not discriminate between the sexes

Barbara Drinkwater, a public health expert at the Pacific Medical Center, debunked some popular myths about osteoporosis. The number one myth is that only postmenopausal women lose bone density, and thus only women need to worry about osteoporosis. In fact, older men are the fastest growing population at risk for osteoporosis. Thirty percent of all hip fractures occur in men. Though typically men are affected at a later age than women, due to a more gradual decline in their sex hormones, male spinal bone loss starts already in middle age, and is significant enough to eventually result in the phenomenon of a stooped "little old man." Thus it is not just the proverbial "little old lady" who suffers from osteoporosis.

The saddest fact is that 80% of osteoporosis victims are undiagnosed and go untreated. Furthermore, surveys have shown that 90% of women think that taking calcium is enough to prevent osteoporosis. Another large percentage of women believe that exercise alone can save their bones, and that the best bone-building exercise is walking. To test this hypothesis, a 12-month study examined the effect of a one-hour lunchtime walking program on bone density. Unfortunately, the results were negative. However, it was also found that active women have 6% more bone density.

Weight lifting is known to produce an increase in bone mass. Nevertheless, it is premenopausal women who respond faster to stress on the bone, again pointing to the importance of hormones in bone building. There is simply no escaping the conclusion that the most reliable way to prevent osteoporosis is hormone replacement. But this is not the end of the story. The most exciting finding suggests that hormone replacement therapy combined with the right exercise gives the best results: it makes it possible for older women to have bones comparable in mass and strength to those of women in their 20s. This is an example of how an age-related degenerative disorder, once regarded as part of "normal aging," can be entirely prevented and even reversed.

Another way in which exercise has an additive effect is by preventing fractures through developing and preserving a better sense of balance, and thus making falling down less likely. Estrogen replacement likewise improves the sense of balance.

Biphosphonates are an important development for those women who have reasons to avoid estrogen replacement. It is possible, however, that only hormones can maintain the viability of bone cells (osteocytes) responsible for the microarchitecture and resilience of the bone tissue. There is also evidence suggesting that a combination of hormone replacement therapy and biphosphonates has a greater effect on bone density than either one alone.

Unfortunately many women still seem unaware that the dramatic loss of bone mass after menopause is due to the loss of hormones, rather than to sudden dietary calcium deficiency. Only 30% of postmenopausal women choose to stay on hormone replacement therapy for more than one year. Typically these are educated women ("exclusively," one conference participant commented), rather than women with the highest risk factors for heart disease and/or osteoporosis.

Perhaps the introduction of designer estrogens, such as raloxifene, will change all that. Though it is not as effective as standard hormone replacement therapy, raloxifene has proven to dramatically diminish the risk of breast cancer as well as to sustain bone mass. On the other hand, raloxifene has side effects such as hot flashes and blood clots. There is also a theoretical possibility that by interfering with the action of estradiol in the brain, raloxifene might lead to depression and maybe even hasten neurodegeneration. Note that a significant percentage of tamoxifen users complain of depression. And, like tamoxifen, raloxifene may also raise the risk of cataracts and other eye damage. It must be emphasized, however, that this is only a theoretical speculation. We simply do not have the data on long-term effects of raloxifene. In terms of benefits for bone and the cardiovascular system, it is clearly second-rate compared with standard hormone replacement therapy. Women would appreciate other options with proven safety.

A disappointing feature of this lecture was the lack of any mention of the effects of vitamins D, E and K, magnesium, boron, zinc, anti-inflammatory fatty acids, and soy estrogens on bone health. Ipriflavone, a chemically transformed soy phytoestrogen also known by the brand name of Ostivone, has now been documented to prevent bone loss. It is also possible that natural soy phytoestrogens, if taken in a sufficient dose, might have benefits for preserving bone mass.

Centenarians: all in the genes?

An ongoing study of centenarians was the topic of this year's Hayflick lecture. Dr. Eugenia Wang of McGill University in Montreal presented her data on Taiwanese centenarians. Using advanced genetic techniques, she focused especially on the genes involved in apoptosis-the self-destruction of cells that the body wishes to eliminate. These apoptotic genes may be a significant determinant of longevity, since the survival of dysfunctional cells is detrimental to the organism.

Another genetic determinant of longevity is the APOE-2 allele (an allele is a normal variant of a gene). The APOE gene seems to govern the susceptibility to cardiovascular disease and Alzheimer's disease. It is actually a gene coding for the cholesterol transport apolipoprotein E. APOE-2 is twice as frequent in centenarians. Jeanne Calment, who lived to be 122, was found to have APOE-3, which is also regarded as a beneficial allele. These alleles developed late in the human evolution. A fascinating speculation is that perhaps here we are seeing "the grandmother effect": the grandchildren of long-lived grandmothers may have had a survival advantage due to a healthy older woman being available to take care of them (especially if the mother should die in childbirth).

The link between APOE-4 allele and susceptibility to Alzheimer's disease is so strong that it might be worthwhile to seek developing gene therapy for those carrying it. One conference participant, however, claimed that if you eliminate or significantly inhibit inflammation, Alzheimer's disease would not develop. Inflammation can be elimination or sufficiently inhibited by using NSAIDs such as ibuprofen (the new selective NSAIDs such as Celebrex promise to work as well with greater safety), quality fish oil, polyphenols and/or estrogen replacement. Antioxidants are also promising, especially vitamin E, though it should be pointed out that antioxidants often have an anti-inflammatory effect, and this is certainly true of high doses of vitamin E.

The debate over the relative importance of genes vs. environment is by no means over. Currently, scientists lean to the view that about 40 - 50% of one's life expectancy is determined by one's genes. According to Dr. Wang, it seems that there are 20 "master genes" that promote longevity. Her goal is to identify those genes.

Sharing her less formal observations of centenarians, Dr. Wang commented on their striking mental sharpness even at a very old age. As an example, she showed an intricate pair of baby booties made from scratch by a Taiwanese woman aged 100. The same woman also smoked until the age of 76, and chewed carcinogenic bitter nuts. Apparently centenarians tend to be remarkably resistant to cancer.

In her future research, Dr. Wang plans to also examine various behavioral traits associated with centenarians, such as optimism and social connectedness.

Anti-aging vitamins

In a historical first, a panel of experts debated the benefits and safety of vitamins E and C to formulate a consensus statement about raising the these nutrients' RDAs. Animal studies have shown that animals with the highest levels of ascorbate and tocopherol in the plasma live longest. While there is total agreement that these vitamins are extremely important for humans as well, human studies have not produced clear-cut results with respect to doses and benefits.

This is particularly true about the doses of vitamin C. Very low ascorbate levels are associated with higher risk of cardiovascular disease and cancer, but there seem to be no additional benefits beyond a certain minimum. Dr. Paul Jacques, while pointing out the flaws in human studies on risk reduction in cataracts with vitamins C and E, nevertheless presented very compelling data on the reduction in cataract incidence with tocopherol supplementation. While supplementing with vitamin C produced only a small risk reduction, when total vitamin C from both diet and supplements was included, the risk of cataracts went down very considerably-perhaps because the fruit and vegetables containing vitamin C also contain other eye-protective nutrients. It was noted that, in general, people who eat the most vegetables-note that it is vegetables rather than fruit-tend to be the healthiest.

Mark Levine of the National Institutes of Health discussed the thorny issue of the ideal dose of vitamin C. He presented a study done on male human volunteers whose diet was first depleted of ascorbate, with different dosages added later. Not much rise in plasma ascorbate levels was found beyond 200 mg per day (by the way, this oral dose is also 100% absorbed, unlike higher doses). Levine also argued that cells saturate before plasma does, at only 100 mg per day. The exception may be the cells of the retina, which seem to require higher concentrations of ascorbate for antioxidant protection. Diabetics appear to need more vitamin C. Smokers may be another category of people with a special need for a higher intake of vitamin C. We also need to examine the issue in regards to women, people with various chronic illnesses and the elderly who, like the diabetics, have higher serum glucose.

A member of the audience pointed out that larger doses of vitamin C may have important benefits in the gastrointestinal tract. Namely, vitamin C helps prevent the formation of carcinogenic nitrosamines. This alone could be a rationale for a higher dosage. A theoretical argument against doses above 1 gram is that some people may tend to develop kidney stones at this level. Epidemiological studies seem to refute this supposition. In fact it might be beneficial to keep the urine more acidic.

There was a lot of agreement, however, on the cardiovascular benefits of vitamin E. A recent Finnish finding that a mere 50 mg of alpha tocopherol considerably lowered prostate cancer incidence and mortality (by 32% and 41%, respectively) has also raised raised the prospect of significant anti-cancer benefits of vitamin E supplementation. In relation to prostate cancer, we badly need a study that combines 200 mg of selenium with various doses of vitamin E. We also need further research on lycopene and ellagic acid as well. Ellagic acid is a polyphenol found in strawberries and cherries; men eating the most strawberries were found to have the lowest prostate cancer risk, lower than that of men eating the most pizza.

In contrast to the lower-dose arguments, a study on LDL oxidation showed that either 2 grams of vitamin C or 400 mg of vitamin E can double the lag time of lipid peroxidation in the plasma. A slight counterargument to this was that even 25 mg of vitamin E has a detectable effect. As for the question whether vitamins C and E have an antioxidant effect on serum lipids in vivo, measuring the peroxidation products in the urine showed that both vitamins did have an in vivo effect, and that the minimum of vitamin E to obtain a detectable effect was 200 mg.

Dr. Margit Traber from the Packer Lab at Berkeley, an expert on vitamin E, presented an interesting brief lecture showing evidence that the body preferentially retains natural alpha tocopherol, while quickly clearing various isomers that exist only in synthetic vitamin E.

Dr. Traber also raised the possibility that vitamin E may raise the risk of hemorrhagic stroke by acting as a blood thinner. Dr. Simin Meydani said that the anti-clotting effect is not seen at doses below 800 mg, and that in her opinion there was no increased risk. In fact aspirin presents a lot more risk in this regard. The panel reached a consensus that supplementation with vitamin E is safe.

It was also pointed out that perhaps limiting the discussion of vitamins to their antioxidant effects is too narrow, since these fascinating compounds also have a wide range of non-antioxidant effects, such as anti-inflammatory action and the newly discovered role in gene expression. The label "antioxidants" may be too narrow, just as the term "sex hormones" does not begin to indicate the enormous metabolic role of those crucial steroids.

One member of the audience raised an interesting point about the importance of how experts act rather than what they say. He suggested that the public is aware that scientists and physicians take supplements of vitamin E themselves, even though they may sound very conservative in their official statements. Consequently the public is likely to conclude that what really counts is what the scientists do to safeguard their own health, rather than what they say, and act on that basis.

Some health enthusiasts would no doubt find the overall tone of the panel to be conservative and minimalist. The arguments for the relatively low dosage of vitamin C were fairly convincing, however. In regard to vitamin E, it was disappointing to see no weight given to the finding that it takes a minimum of 400 mg to protect LDL cholesterol from oxidation, and that levels even higher than that might be more optimal. No mention was made of the Packer Lab findings that vitamin E can dramatically slow down aging at the cellular level.

Ultimately, the panel reached the conclusion that the RDA for vitamin C should be raised to 200 mg/day, and this intake is best secured from vegetables and fruit, since these provide additional valuable nutrients. However, the panel concluded that the RDA for vitamin E should likewise be raised to 200 milligrams a day, and that only supplements can provide this level. There is simply no safe and practical way to obtain this amount from the diet. In effect, this is an admission that even the best possible diet cannot supply all the nutrients needed for optimal function, particularly by the elderly.

The irony of the situation is that people who take supplements already tend to eat a good diet. It is the poor and the smokers who most need to take supplements. Durk Pearson raised a provocative point that it is expensive for the average family to consume the recommended five or more servings of vegetables and fruit, especially in winter. This is obvious if we think of blueberries. Thus, relatively inexpensive supplements might have a considerable impact on the health of the less affluent population. Dr. Bruce Ames also suggested that officially recommending a multivitamin might be a good place to start in the hope of improving the health of the less-educated. Since obesity and smoking are also more prevalent among these segments of the population, such a recommendation would be a band-aid approach, but at least it would be a start.

Ultimately, though, antioxidant intake can only do so much. Taking antioxidants is basically aimed at trying to lower the degree of damage that comes from free-radical production. We also need to do something about caloric consumption, smoking, and excess levels of stress. In other words, we need to look at the initiation end of the spectrum. Most production of free radicals takes place in the mitochondria, so it is vital to preserve efficient mitochondrial metabolism. Unfortunately, at this point calorie restriction remains the only proven way to extend maximal life span. However, we are gaining knowledge of compounds such as lipoic acid and carnitine, already documented to restore mitochondrial efficiency.

At the threshold of real breakthroughs

Many participants have commented on the excellent and exciting quality of this year's AGE conference. One of the problems facing American gerontology has been the official policy that the aging process should be studied, but not for the purpose of intervention. This conference, however, presented a wealth of data with inescapable implications for the prevention of aging-related degenerative disorders such as Alzheimer's disease, heart disease, immune decline, cancer, cataracts, osteoporosis and more. In fact, a whole day was devoted to various approaches for altering the aging process.

Not acting on our growing knowledge of how to prevent the suffering and disability associated with aging would be highly questionable from the point of view of ethics. Even simple steps, such as recommending the daily consumption of blueberries or other berries and raising the RDA's for various nutrients, might have extremely significant impact on public health. The fact that the panel of experts officially recommended raising the RDA's for vitamins C and E is thus of historical importance. It amounts to a public admission by the scientific community that we can do something about aging.

In addition, there is now little doubt that the near future will bring further exciting breakthroughs in the form of gene therapy, anti-glycation products, and ways to mimic calorie restriction. At long last, we can be truly optimistic about our chances to live a very long, vigorous and disease-free life.

Blueberry Power: Phytonutrients and the Brain

It is well known that certain foods such as berries and spinach provide a wealth of potent antioxidants. Eating a cup of blueberries, for instance, can double a typical American daily antioxidant intake. This may have tremendous implication for the prevention of free radical-related disorders, including neurodegenerative diseases.

One of the phenomena of aging is a decreased release of dopamine, a neurotransmitter crucial for mood, motivation and motor control. Higher dopamine may also indirectly lead to lower insulin levels. It is interesting that some proven anti-aging agents seem to work precisely by increasing dopamine levels. A team of researchers from Tufts University presented evidence showing that a diet enriched with blueberries can increase dopamine release in rats. The practical consequence of this was improved performance on motor tests, such as the difficult task on staying on a rotating rod.

Blueberries contain various anthocyanins, a subcategory of flavonoids responsible for the deep blue color of blueberries. Anthocyanins are also known to be potent antioxidants, and have an anti-inflammatory action as well. In addition, they have been found to increase membrane fluidity and to act as blood thinners.

In response to a question about the relative antioxidant potencies of blueberries as compared to bilberries, the speaker said that some of the wild varieties of blueberries were "almost as good" as the European bilberries. Her team may eventually run a comparison between blueberry extract and bilberry extract.

There is a fruit that comes close to the antioxidant power of blueberries: prunes. A few prunes a day might indeed keep Alzheimer's disease away, but, as the Tufts researchers pointed out, prunes have a PR problem. Blueberries, on the other hand, "are elegant, like Princess Di."

Spinach was also shown to be effective in preventing age-related dopamine decrease, and maintaining the ability to remove calcium ions from the cell. Spinach helped with water maze performance, possibly because this task requires visual input, and spinach is known to preserve vision.

Rick Weindruch raised an interesting point concerning the use of a purified diet in nutritional research. He suggested that the purified diet is so deficient in antioxidants that the dramatic effect of the blueberry-enriched diet might be due to making up for these deficiencies. While the effect of frequent blueberry consumption might indeed not be as dramatic in humans who already eat an antioxidant-rich diet, the documented benefits of anthocyanins seems at least as promising as those of green tea polyphenols.

Considering the high cost of blueberries, I asked a couple of chemists if frozen blueberries, or frozen berries in general, have the ability to provide benefits similar to those of fresh berries. The chemists agreed that frozen berries should still provide considerable benefits. -IG


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