Kelvin Davies, associate dean and holder of the James E. Birren Chair of Gerontology at the USC Davis School of Gerontology, has received a $244,000 American Recovery and Reinvestment Act grant from the National Institutes of Health for research on oxidative stress and aging.
Funds will be used to conduct research on several genetic regulators of large protein complexes known as proteasomes that help to mitigate the harmful effects of oxidative stress.
Cells use proteasomes to degrade unneeded, damaged or improperly folded proteins.
“We have identified several important proteasomal activators in our system,” said Davies, also a professor of molecular and computational biology at USC College. “One we initially discovered was expected to play a unique role during oxidative stress adaptation, but we also found three others that modify the degradation of oxidized proteins either by binding to the proteasome or by binding to oxidized proteins, or both.”
The research also revealed that the proteasome activators undergo increased synthesis as cells adapt to higher levels of oxidative stress. The question, Davies said, is whether older cells, or cells from older people, can increase their production of the proteasome activators to effectively adapt to oxidative stress.
Further research is aimed at better understanding the role of proteasomes in minimizing the damaging effects of oxidative stress.
Oxidation causes cellular proteins to lose activity or function, to unfold and to aggregate together to form intracellular inclusion bodies. The loss of important functions and the formation of aggregates and inclusion bodies are all damaging to cells and appear to play roles in such age-related diseases as Alzheimer’s and Parkinson’s, heart attacks, strokes, cancer and diminished/altered immune function.
The results in Davies’ lab come on the heels of other breakthroughs which have established that protein turnover, or the balance between the synthesis and degradation of proteins, changes as people age. As people get older, a decline in protein turnover is accompanied by a steep increase in the number of oxidized proteins, which inhibit the proteasome.
“We now propose two years of additional research in order to properly pursue these exciting preliminary findings,” Davies said. “The grant seeks to accelerate the pace and achievement of our research, to create new jobs and to purchase much-needed equipment.”
Davies expects to hire one new postdoctoral researcher and up to two new research assistants with Recovery Act funds.
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