Many scientists have wondered whether a single cause (probably cellular or hormonal) lies behind all aging phenomena — or whether aging is inherently multi-faceted. Differences in lifespan between species raise critical questions, in this regard. Why is a rodent old at 3 years, a horse old at 35 years and a human old at 80 years? Aren't the cells much the same? Why is it that at age 3 about 30% of rodents have had cancer, whereas at age 85, about 30% of humans have had cancer? Some species (such as lobsters, alligators and sharks) show few signs of aging. Cancer cells, stem cells and human germ cells seem "immortal" when compared to other cells.
When discussing aging it is important to distinguish two points on survival curves. Mean lifespan (average lifespan) corresponds to the age at which the horizontal line for 50% survival intersects the survival curve. Maximum lifespan corresponds to the age at which the survival curves touch the age-axis (0% survival) — and this represents the age at which the oldest known member of the species has died. (In animal studies, maximum lifespan is typically taken to be the mean lifespan of the most long-lived 10%.) Curve A as shown is a pure exponential decay curve. Curve B corresponds to the survival of small animals, such as mice or squirrels in a natural environment. Human survival was still close to curve B in ancient Rome when average lifespan was 22 years, but by the mid−1800s the typical North American lived to be 40 — more like curve C. Today, people in the most developed countries have an average lifespan of about 80 — resembling curve D. Reduction of infant mortality has accounted for most of the increased longevity, but since the 1960s mortality rates among those over 80 years has been decreasing by about 1.5% per year. Maximum lifespan for humans, however, has remained about 115−120 all through known history. The longest documented human lifespan has been for Frenchwoman Jean Calment who lived 122.3 years.
Curing specific diseases such as heart disease or cancer can do no more than further "square" the survival curve (toward curve E), with no effect on maximum lifespan. Curing cancer would add about 2 years to human life, whereas eliminating heart disease would add 3 or 4 years. Mean lifespan varies with susceptibility to disease, accident & homicide/suicide, whereas maximum lifespan is determined by "rate of aging". In aging research, maximum lifespan is regarded as a proxy for aging. Chemicals, calorie restriction with adequate nutrition, or other interventions which increase maximum lifespan are said to have slowed the aging process.
If human beings were free of disease & senescence the only causes of death would be accident, suicide & homicide. Under such conditions it is estimated that from a population of one billion, a 12-year-old would have a median lifespan of 1,200 years and a maximum lifespan of 25,000 years.In 1825 an English actuary named Benjamin Gompertz discovered that likelihood of dying increases exponentially with age after maturity — an empirical observation that has stood the test of time. A 35-year-old is twice as likely to die as a 25-year-old and a 25-year-old is twice as likely to die as a 15-year-old. The exponential increase does not continue past age 80 and death rate may even decline after age 110 [SCIENCE 280:855-860 (1998)]. (Medflies — Mediterranean fruit flies — show a plateau of linear rather than exponential death rate when 20-25% of the population remains). Similarly, the risk of getting Alzheimer's Disease doubles every 5 years past the age of 60 — probably plateauing after age 90 (when over half the population is already demented). Cancer rate increases exponentially with age, but also seems to plateau in the very elderly. One explanation might be that subsets of the population that are considerably more hardy due to genetics or behavior may remain after the more heterogenous majority have died. Another explanation suggests the complete elimination of the forces of natural selection at the oldest ages — which causes subsequent survival to be completely the result of genetic "random drift" [PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (USA) 93:15249-15253 (1996)]. Causes of death in middle-age tend to be due to diseases affecting high-risk individuals (cancer, diabetes, hypertension, etc.), whereas the elderly are more vulnerable to multiple pathologies due to vulnerability of aging organs &
tissues [JOURNALS OF GERONTOLOGY 58A(6):B495-B507 (2003)].
Attempts to classify theories of aging have led to the two major classifications programmed aging and wear&tear aging. Programmed aging would be aging due to something inside an organism's control mechanisms that forces elderliness & deterioration — similar to the way genes program other life-stages such as cell differentiation during embryological development or sexual maturation at adolescence. By contrast aging due to wear&tear is not the result of any specific controlling program, but is the effect of the sum effect of many kinds of environmental assaults — ie, damage due to radiation, chemical toxins, metal ions, free-radicals, hydrolysis, glycation, disulfide-bond cross- linking, etc. Such damage can affect genes, proteins, cell membranes, enzyme function, blood vessels, etc.
When Pacific salmon have lived in the ocean for 2 or 3 years, they make an arduous upstream journey against a raging riverswim until they find a place suitable for spawning. After spawning, the adrenal gland releases massive amounts of corticosteroids — leading to rapid deterioration. It would be costly for the species to have salmon that could live another year and repeat the journey — or compete with the offspring for food. Although this process is obviously "programmed", it is inaccurate to describe it as "aging". Programmed death, rather than programmed aging, is a common phenomenon among animals that reproduce only once.
Grazing animals show wear-and-tear to their teeth to the point where they can no longer eat, and they die of starvation. Again, it stretches the point to say the teeth are aging. The teeth of rabbits (like human fingernails) continue to grow as wearing occurs — and in this sense are "programmed" to compensate for "wear&tear". Why don't grazing animals have teeth that continue to grow? Human beings can replace tissue, capillaries and bone in wound-healing, yet cannot regrow a severed limb the way a salamander can. Why isn't human DNA "programmed" to re-grow kidney or liver tissue as it ages? Planarians (flatworms) have a pool of stem cells which can replace any of their fully differentiated cells. Programming that compensates for wear & tear should be distinguished from programming that causes deterioration.
Xanya Sofra Weiss
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