Info

diabetic retinopathy

All systems

Cancer

Vitamin or micronutrient

Vitamins B6, E copper, zinc, and selenium

Vitamins C, E, and carotenoids

Carotenoids and zinc

Selenium

Vitamin C, ^-carotene, «-tocopherol, and zinc of, and develop strategies for using various classes of antioxidants to reduce the effects of aging. Other dietary components may also have a beneficial effect in preventing or delaying the onset of age-related disease. For example, as a deterrent against the onset of osteoporosis, adults should ensure adequate calcium and vitamin D intakes.

Dietary energy restriction The effect of caloric restriction on life span has only been convincingly demonstrated in rodents to date. Feeding mice and rats diets that are severely deficient in energy (about 35% of that of animals fed ad libitum, after the initial period of growth) retards the aging of body tissues, inhibits the development of disease and tumors, and prolongs life span significantly. The exact mechanism of action of dietary energy restriction remains to be elucidated, but may involve modulation of free radical metabolism, or the reduced hormone excretion that occurs in dietary restricted animals may lower whole body metabolism resulting in less 'wear and tear' to body organs and tissues.

Current investigations into the effects of dietary energy restriction (of about 30%) on the life spans of primates, squirrels, and rhesus monkeys continue. Caloric restriction in rhesus monkeys leads to reductions in body temperature and energy expenditure consistent with the rodent studies. These investigations should have direct implications for a dietary energy restriction intervention aimed at slowing

Table 4 Effects of vitamins and micronutrients on age-related disorders

Vitamin or micronutrient

Vitamins B6, E copper, zinc, and selenium

Vitamins C, E, and carotenoids

Carotenoids and zinc

Selenium

Vitamin C, ^-carotene, «-tocopherol, and zinc

Selenium, copper, zinc, lithium, vanadium, chromium, and magnesium Vitamins B12, B6, and folate

Chromium

Possible effect on age-related disorder

Impairment of immune function in older humans if inadequate amounts Increased amount in the diet is associated with delayed development of various forms of cataract Protective effect against the development of lung cancer in smokers Dietary supplementation associated with a decreased risk of age-related macular degeneration Absolute or relative deficiency associated with development of a number of cancers (not breast cancer) Dietary supplementation may decrease the rate of development of atherosclerosis Dietary deficits are associated with an increased risk of cardiovascular disease

Adequate levels throughout a lifetime may prevent some of the age-related decrease in cognitive function Deficiency is associated with an increased risk of the development of type 2 diabetes mellitus down the aging process in humans, should any humans wish to extend their life span at such a cost. Once the mechanisms of effects of caloric restriction on longevity are understood it may be possible to develop drugs that act through these mechanisms directly, mitigating the need for diets that interfere with the quality of life.

Molecular Biological Interventions and the Aging Process

Accelerated aging syndromes show degenerative characteristics similar to those appearing during normal aging. The mutations leading to these disorders are being identified and their roles in the aging process are being elucidated. Examining differences in the genetic material from normal elderly people and those with progeria should help to give a better understanding of the genetic mechanisms of aging. Identification of a control gene or genes that inhibit the action of the genes producing the progeroid phe-notype might make it possible to slow down aberrant protein production in normal people as well.

As an example, the genetic defect that predisposes individuals to the development of Werner's syndrome has now been elucidated. Individuals with this disease carry two copies of a mutant gene that codes for a helicase enzyme (helicases split apart or unwind the two strands of the DNA double helix). DNA helicases play a role in DNA replication and repair.

In light of the biological function of these enzymes it has been proposed that the reason for the premature aging in Werner's syndrome is that the defective helicase prevents DNA repair enzymes from removing background DNA damage, which thus becomes fixed as mutations, with consequent deleterious effects on cellular function. It remains to be determined whether increasing the fidelity or activity of helicases in cells will extend their life span.

Since it appears that the loss of telomeric DNA sequences can lead to replicative senescence in dividing cells, in theory by preventing such telomere loss the life span of the cell could be extended. A naturally occurring enzyme, telomerase, exists to restore telomeric DNA sequences lost by replication. Telo-merase is normally only functional in germ cells. Manipulating certain cell types (e.g., cells of the immune system) to regulate the expression telomer-ase may extend their functional life span. Drugs that enhance telomerase activity in somatic cells are currently being developed. However, cellular senescence has been implicated as a tumor suppressor mechanism and it has been found that cancer cells express telomerase. An uncontrolled expression of this enzyme in somatic cells may lead to the onset of malignancy through uncontrolled cell proliferation. Thus, any intervention aiming to increase life span based on the cellular expression of telomerase must strike a balance between maintaining controlled cell division and uncontrolled proliferation.

A number of single gene mutations have been identified that affect metabolic function, hormonal signaling, and gene silencing pathways. In the future it may be possible to develop drugs to mimic the antiaging effects that these genes exert.

See also: Antioxidants: Diet and Antioxidant Defense; Observational Studies; Intervention Studies. Cancer: Epidemiology and Associations Between Diet and Cancer. Coronary Heart Disease: Lipid Theory; Prevention. Fats and Oils. Fatty Acids: Monounsaturated; Saturated. Growth and Development, Physiological Aspects. Lipids: Chemistry and Classification; Composition and Role of Phospholipids. Nucleic Acids. Nutrient Requirements, International Perspectives. Older People: Nutritional Requirements; Nutrition-Related Problems; Nutritional Management of Geriatric Patients. Protein: Synthesis and Turnover; Requirements and Role in Diet; Digestion and Bioavailability. Supplementation: Role of Micronutrient Supplementation.

How to Stay Young

How to Stay Young

For centuries, ever since the legendary Ponce de Leon went searching for the elusive Fountain of Youth, people have been looking for ways to slow down the aging process. Medical science has made great strides in keeping people alive longer by preventing and curing disease, and helping people to live healthier lives. Average life expectancy keeps increasing, and most of us can look forward to the chance to live much longer lives than our ancestors.

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