| Though currently mechanisms driving aging and age-related diseases are unclear, many longevity manipulations have been demonstrated to delay aging and extend lifespan in animal models. Thus, elucidating the mechanism of these manipulations would help to better understand aging itself and to prevent aging-associated diseases. To clarify theses mechanisms, RNAi screenings were designed and performed to find out which genes play a role in longevity regulation. In these studies, we discovered that a transcription co-activator, CBP-1, was required for the life-extending effect of dietary restriction (DR) and the insulin-signaling pathway. Inhibition of cbp-1 blocked lifespan extension and accelerated the aging process. Three potential CBP-1 binding proteins, DAF-16, HSF-1 and DVE-1, were also required for the effect of DR to extend lifespan. Thus, a transcriptional complex composed of CBP-1 and its binding partners regulates the aging process and longevity. Furthermore, we also discovered that XPC-1, a nucleotide excision repair protein, regulated resistance to oxidative stress and lifespan. Inhibition of xpc-1 increased resistance to oxidative stress, extended lifespan and slowed the rate of aging. Further studies are needed to clarify the role of XPC-1 and to understand the link between DNA damage repair and aging. |
