PPARγ Accumulation and Metabolic Decline in Aging

The association of aging with the metabolic syndrome remains unexplained. The PI proposes to investigate a novel mechanism linking insulin resistance with aging, with the aim to identify novel and safer interventions for age-associated metabolic diseases. PPARγ is a master regulator of adipocyte formation and function, and plays a pivotal role in metabolism and insulin action, but its role in aging is unknown. The PI demonstrated a remarkable increase of PPARγ in tissues from aging individuals and aging experimental animals, along with stark differences in the response to the PPARγ ligand thiazolidinedione (TZD) in young vs. aging animals. He hypothesized that the accumulation of PPARγ contributes to the metabolic decline during aging. He proposed to establish the physiological significance of PPARγ accumulation in aging and elucidate its molecular basis. The ultimate goal of this work is to identify new mechanisms connecting aging and metabolic syndrome and provide novel therapeutic candidates for delaying the onset of metabolic diseases in aging.