Evolution of senescence: Longevity and the expression of heat shock proteins

Senescence is the progressive deterioration of organismal function leading to accelerating rates of mortality. Cumulative extrinsic and intrinsic stre sses are thought to contribute to senescence. Molecular chaperones, such as heat shock proteins, are hypothesized to modulate senescence through their ability to mitigate protein damage. Recent discoveries made with the nemat ode Caenorhabditis elegans and the fruit fly Drosophila melanogaster lend s trong support to this theory. Longevity extending mutants of the nematode a lso increase intrinsic and inducible thermotolerance, and they overexpress heat shock proteins upon thermal shock. Intriguingly, these genes regulate dauer (diapause) formation, and are associated with an insulin-like depende nt signal transduction pathway. Direct evidence for a casual role of hsp70 in aging is provided by analysis of transgenic fruit flies. When hsp70 is i nduced by mild heat shock, flies that overexpress the protein have greatly reduced mortality rates during subsequent weeks of aging at normal temperat ures. Current work with fruit flies focuses on the relationship between ins ulin-like receptors, ovarian diapause, heat shock and aging.