[
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
[
1987]
Since the last review in this series [Johnson, 1985], many papers have appeared dealing directly with the aging process in both Caenorhabditis elegans and Turbatrix aceti. We will review this work and also briefly review other areas of C. elegans research that may impact on the study of aging. C. elegans has become a major biological model; four "News" articles in Science [Lewin, 1984a,b; Marx, 1984a,b] and inclusion as one of three developmental genetics models in a recent text [Wilkins, 1986] indicate its importance. Recent work has verified earlier results and has advanced progress toward new goals, such as routine molecular cloning. The aging studies reviewed here, together with new findings from other areas of C. elegans research, lay the groundwork for rapid advances in our understanding of aging in nematodes. Several areas of research in C. elegans have been reviewed recently: the genetic approach to understanding the cell lineage [Sternberg and Horvitz, 1984] and a brief summary of cell lineage mutants [Hedgecock, 1985]. The specification of neuronal development and neural connectivity has been a continuing theme in C. elegans research and reviews of these areas have also appeared [Chalfie, 1984; White, 1985]. A major genetic advance is the development of reliable, if not routine, mosaic analysis [Herman, 1984; Herman and Kari, 1985], which is useful for the genetic analysis of tissue-limited gene expression. Hodgkin [1985] reviews studies on a series of mutants involved in the specification of sex. These include her mutations that cause XO worms (normally males) to develop as hermaphrodites and tra mutations that change XX hermaphrodites into phenotypic males. The work on the structure and development of nematode muscle has been summarized by Waterston and Francis [1985]. A comprehensive review of aging research, containing useful reference material on potential biomarkers, has appeared [Johnson and Simpson, 1985], as well as a review including