The adapter protein Shc, which couples mitogenic signals from cell surface receptors through the Ras/MAPK pathway, has recently been implicated as a determinant of mammalian longevity, as mice harboring a targeted knockout of p66^shc live 30% longer than control littermates. In addition to long life, p66^shc KO mice exhibit...

One major advance in the study of mammalian aging was the discovery made by Hayflick in the 1960's. He observed that normal human cells had a finite lifespan in vitro and could execute only a limited number of cell divisions. Beyond this limit, cells undergo an irreversible growth arrest known as replicative senescence, or M1 (mortality-...

Accumulation of DNA damage and loss of telomere protection contribute significantly to the aging process. The Nbs1, Mre11 and Rad50 complex (NMR) plays an important role in DNA double strand break (DSB) repair and telomere maintenance. Two components of this complex, Nbs1 and Mre11, are mutated in Nijmegen breakage syndrome (NBS), and...

The most effective experimental way to prolong lifespan and slow aging in rodents is to limit their calorie intake by feeding them a controlled balanced diet, a regimen known as calorie restriction (CR). Since calorie restricted animals undergo a reduction of their core body temperature (CBT), it was hypothesized that reduction of CBT could...

Overview. Living in an aerobic world, oxidative stress has been implicated in the aging process and in the development of a number of age-related, neurological diseases. An organism, however, has means to detoxify reactive oxygen species, including the enzymes glutathione peroxidase, superoxide dismutase, and catalase. When reactive...

The present proposal is aimed at testing the hypothesis that activation of brain specific Uncoupling Proteins (UCPs) could prove chronically neuroprotective by providing a combination of two protective measures a) reducing free radical formation, b) reducing the vulnerability of mitochondria to excitotoxic glutamate mediated overloading with...