Life Extension

Life Extension - updated: 23 February 2009

The biology of aging

Mt Sinai J Med. 2003 Jan;70(1):3-22

Troen BR.

In humans, aging is inexorable. The progressive decrease in physiological capacity and the reduced ability to respond to environmental stresses lead to increased susceptibility and vulnerability to disease. Consequently, mortality due to all causes increases exponentially with aging. Attempts at understanding the causes of aging are limited by the complexity of the problem. Aging changes are manifest from the molecular to the organismic level; environmental factors affect experimental observations; secondary effects complicate elucidation of primary mechanisms; and precisely defined, easily measurable biomarkers are lacking. No one unifying theory may exist, since the mechanisms of aging could be quite distinct in different organisms, tissues, and cells. Evolutionary pressures have selected for successful reproduction, making it likely that the post-reproductive physiology of an organism (i.e., aging) is an epigenetic and pleiotropic manifestation of the optimization for early fitness. Indeed, antagonistic pleiotropy, wherein genes that enhance early survival and function but are disadvantageous later in life, may play an overriding role in aging. Theories of aging can be divided into two general categories: stochastic and developmental-genetic. These are not mutually exclusive, particularly when considering the free radical/mitochondrial DNA theory of aging. Increasing evidence suggests that cellular senescence and organismic aging are antagonistically pleiotropic manifestations of evolutionary pressures to prevent malignant transformation. In other words, aging may be the price we pay to avoid cancer. The beneficial paradox may be that the maximum lifespan potential of humans may have been achieved, in part, due to our ability to grow old.

Publication Types:

• Review

On maximum human life span: interdisciplinary approach about its limits

Adv Gerontol. 2005;16:14-20

Ruiz-Torres A, Beier W.

BACKGROUND: This is a theoretical approach on the question on how much maximally may extend the life of human individual. The starting point of this work was the biological consideration of two changes in human characteristics which took place during the last century up to now, namely human beings lived remarkably longer and are becoming taller. METHODS: Demography data and Gompertz deduced mathematics, either related to growth or survival, were the two columns on which the basis of this study has been supported. Respective equations were adapted to the purpose searched applying parameters of. normal body growth and cell growth in vitro. Having individual age on the abscisse, that of its crossing point with ordinate value indicates the age in which no more cell activity should exist, either of proliferation or migration. RESULTS: Despite rising life expectancy, whose extrapolation leads to remarkable enhance for future values, life span calculations with the help of our mathematic models do not indicate an extent beyond the limit of 120 years. Nevertheless hypothetically there is the exception of prolonging life out of the mentioned limit when growth and ageing would be proportional interrelated. Furthermore, when proliferation results of in vitro smooth muscle cell cultures were related to age of donor, its linear regression crosses the x-axis at an age of 110.16 years (mean value of different procedures of measurement) . This limit is not far from that using other cell activity parameters as migration (117.7 years when cessation) or such state of senescent (98 years when all cells involved). Nevertheless with the help of Gompertz equation putting growth in the ordinate (proliferation activity) instead mortality and donor age in the x-axis, the follow up of the curve is similar to that known of survival up to the age of 80. But this procedure does not seem adequate to obtain information on the limit of life potential because of later this curve becomes very flat reaching the end at age around 180; this seems not to be real but due to an artefact. Finally IGF-1 prolongs the cessation ( x-axis crossing point) of cell growing activity up to donor age of around 126.4 years. CONCLUSIONS: Human life span seems to be limited up to around 120 years, but growth process modulating factors could theoretically enhance it.

Publication Types:

• Review

Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging

Clin Interv Aging. 2006;1(3):261-5

Janson M.

Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes, cardiovascular disease, hypertension, congestive heart failure, age-related deterioration of brain function and vision, and immune function, as well as other age-related health problems.

Publication Types:

• Review

Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging

Clin Interv Aging. 2006;1(3):261-5

Janson M.

Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes, cardiovascular disease, hypertension, congestive heart failure, age-related deterioration of brain function and vision, and immune function, as well as other age-related health problems.

Publication Types:

• Study

Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging

Clin Interv Aging. 2006;1(3):261-5

Janson M.

Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes, cardiovascular disease, hypertension, congestive heart failure, age-related deterioration of brain function and vision, and immune function, as well as other age-related health problems.

Publication Types:

• Study

Micronutrients prevent cancer and delay aging

Toxicol Lett. 1998 Dec 28;102-103:5-18.

Ames BN.

Approximately 40 micronutrients are required in the human diet. Deficiency of vitamins B12, folic acid, B6, niacin, C, or E, or iron, or zinc, appears to mimic radiation in damaging DNA by causing single- and double-strand breaks, oxidative lesions, or both. The percentage of the US population that has a low intake (< 50% of the RDA) for each of these eight micronutrients ranges from 2% to > or = 20%; half of the population may be deficient in at least one of these micronutrients. Folate deficiency occurs in approximately 10% of the US population, and in a much higher percentage of the poor. Folate deficiency causes extensive incorporation of uracil into human DNA (4 million/cell), leading to chromosomal breaks. This mechanism is the likely cause of the increased cancer risk, and perhaps the cognitive defects associated with low folate intake. Some evidence, and mechanistic considerations, suggest that vitamin B12 and B6 deficiencies also cause high uracil and chromosome breaks. Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables (five portions a day is advised) has approximately double the cancer rate for most types of cancer when compared to the quarter with the highest intake. Eighty percent of American children and adolescents and 68% of adults do not eat five portions a day. Common micronutrient deficiencies are likely to damage DNA by the same mechanism as radiation and many chemicals, appear to be orders of magnitude more important, and should be compared for perspective. Remedying micronutrient deficiencies is likely to lead to a major improvement in health and an increase in longevity at low cost. Aging appears to be due, in good part, to the oxidants produced by mitochondria as by-products of normal metabolism. In old rats mitochondrial membrane potential, cardiolipin levels, respiratory control ratio, and overall cellular O2 consumption are lower than in young rats, and the level of oxidants (per unit O2) is higher. The level of mutagenic aldehydes from lipid peroxidation is also increased. Ambulatory activity declines markedly in old rats. Feeding old rats the normal mitochondrial metabolites acetyl carnitine and lipoic acid for a few weeks, restores mitochondrial function, lowers oxidants to the level of a young rat, and increases ambulatory activity. Thus, these two metabolites can be considered necessary for health in old age and are therefore conditional micronutrients. This restoration suggests a plausible mechanism: with age-increased oxidative damage to proteins and lipid membranes causes a deformation of structure of key enzymes, with a consequent lessening of affinity (Km) for the enzyme substrate; an increased level of the substrate restores the velocity of the reaction, and thus restores function.

Publication Types:

• Review

Publication Types:

• Review