Dear Editor,Aging in metazoans is a complex process associated with declining ability to respond to stress or maintain homeostasis, and an increased risk of disease. Studies of aging in several model systems have revealed remarkable similarities in the cellular pathways influencing lifespan determination among a range of organisms including fungi, invertebrates and mammals. The fruit fly Drosophila melanogaster has served as an excellent model organism for studies of the aging process, due in part to its short generation time, ease of genetic manipulation, and the apparently conserved aging pathways it shares with other organisms. 1 Dietary restriction (DR) has been shown to robustly extend the lifespan of phylogenetically diverse organisms, suggesting that nutrient regulation of metabolism and aging act through conserved pathways. While the mechanisms by which DR extends lifespan are unclear, a role for the conserved TOR pathway has been suggested. [2][3][4] TOR is serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis and translation. 5 TOR is a central component in the regulation of growth and metabolism in response to nutrient conditions and developmental state. TOR is a serine/threonine kinase subunit of TORC1 and TORC2. 5 TORC1 regulates a number of metabolic activities thought to influence aging including translation and ribosome biogenesis, metabolism and autophagy. 6-8 TORC1 activity is repressed by low nutrient levels or reduced growth factor signaling, two conditions known to increase lifespan, 1,7 and there is experimental support for the theory that TORC1 regulates aging in response to nutrient input. 2-4 Mutants affecting the Caenorhabditis elegans homolog of the TORC2 component Rictor were recently shown to affect lifespan in a nutrient-sensitive manner, suggesting that TORC2 functions in nutrient-regulated aging in nematodes. 9The drug rapamycin has been used as a potent and specific inhibitor of TOR activity for studies in cultured cells. Rapamycin binds to cytosolic FK-binding protein 12 (FKBP-12) and the rapamycin-FKBP12 complex Figure 1 Demographic patterns in flies maintained on food containing rapamycin. Female (a) and male (b) survivorship when maintained on different concentrations of rapamycin.The concentration of rapamycin in the food is indicated in each legend. Survivorship is plotted with data of three replicate cages for each treatment combined.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.