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Molecular Biology of Aging,
1999]
"Gerontogenes" (genes that affect the rate of aging) can be defined operationally to refer to genes that can be altered such that a longer than normal maximum lifespan is the result. The last two decades of research in aging have demonstrated overwhelmingly that gerontogenes exist and modulate the rate of aging. The first direct demonstration that genes play a role in the aging process was carried out in the nematode Caenorhabditis elegans. Despite original prejudices that the aging process is "ineluctable" or that genes controlling longevity cannot be selected for, these results and others have shown that the process of aging, just as other biological processes, is specified by the gene. This is not to say that aging is programmed. Statements by noted developmental biologists that aging must be programmed to prevent competition with offspring are untenable for the nematode C. elegans, which has billions of descendents by the time its hypothetical "death program" kicks in to kill it. In the text below I will provide an overview, first of work primarily from my laboratory having to do with the detection and study of gerontogene variants using multigenic approaches. Subsequent work on mutants, initially from my lab but more recently from a variety of other labs as well, showing the molecular nature of these gerontogenes will be subsequently reviewed. Finally, we will close with a discussion of the role of resistance to stress in determining life-extension: a hypothesis that is gaining increasing support from a wide variety of observations in both invertebrate and vertebrate