Selection And Demographic Experiments

In 1957, G.C. Williams proposed antagonistic pleiotropy as an explanation for the evolution of aging (Williams, 1957). According to the theory, the declining force of selection with age results in selection for pleiotropic genes that enhance fitness early in life but reduce it later. The accumulation of many such genes could result in a deterioration of condition with age. This hypothesis became a driving force for most evolutionary studies of aging. Current research on the topic is less explicitly genetic, referring more to ''trade-offs'' than ''pleiotropy'': a recognition that constraints may come from physiological, developmental, or even behavioral conflicts.

Because of its short generation time, Drosophila is ideally suited to selection experiments testing trade-off hypotheses. In a series of seminal experiments, Rose (1984) confirmed antagonistic pleiotropy for aging in Drosophila, demonstrating a tight correlation between early fecundity and lifespan. Selection for early fecundity produced short lifespans; selection for late fecundity produced long lifespans. Moreover, the results were highly reproducible. Further experiments in a number of labs have examined other trade-offs with lifespan. Development time was found to not be directly associated with lifespan, disproving the developmental theory of aging (Lints, 1978), at least for Drosophila (Chippindale et al., 1994). Stress resistance was found to correlate positively with lifespan, though this response could eventually be broken down with strong selection over many generations (Phelan et al., 2003). Mating itself was found to be toxic to females, mediating the lifespan-fecundity trade-off (Chapman et al., 1993).

Large population sizes in Drosophila have also facilitated demographic studies examining fine details of mortality rate changes with age. Late-life mortality plateaus, a common phenomenon in a number of species, has been examined in depth in Drosophila. Also, studies have been conducted with large populations testing antagonistic pleiotropy in contrast to simple mutation accumulation, though the interpretation of the results is still debated (Hughes et al., 2002). Both mutation accumulation and antagonistic pleiotropy predict age-specific effects of mutations on mortality; this also has been tested and found (Yampolsky et al., 2000).

It is a testament to the strength of the Drosophila model that most of the above studies, especially the detailed demographic explorations of mortality, have been done only in Drosophila. However, this also produces the caveat that the results may apply only to Drosophila, or at least may apply less broadly than some of the genetic mechanisms of aging described below. For example, while there do appear to be trade-offs between reproduction and longevity in mammals, the correlation is much less tight than in Drosophila and the mechanisms may be indirect (Cohen, 2004).

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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