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The Role of Apoptosis and Scescence in Aging Models

$26,729F32FY2004AGNIH

University Of Calif-Lawrenc Berkeley Lab, Berkeley CA

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Abstract

DESCRIPTION (provided by applicant): The cellular processes of apoptosis and senescence share many similarities; both are, activated by stress and prevent clonal expansion. The molecular mechanism(s) by which cells decide to undergo apoptosis or senescence is unknown. Furthermore, the significance of this cellular decision at the level of the organism is unknown. This proposal aims to lay the groundwork and begin to test the hypothesis that either of these cellular processes is responsible for organismal phenotypes, specifically the process of aging. Using mouse embryonic fibroblasts from short-lived mouse strains, this study will measure apoptosis, senescence, and proliferation over time. Another aim of this proposal is to influence is primary mouse and human cells away senescence and towards apoptosis, and visa versa, when challenged exogenous tress. This will be accomplished by ectopically expressing genes that regulate apoptosis and senescence. These experiments will give insight into the relationship between apoptosis and senescence, and begin to correlate the affects of cellular decisions and aging.

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