Aging

Aging is a complex process in which fitness and fertility progressively diminish while mortality increases over time. Although aging is observed across the phylogenetic spectrum from yeast to humans, the biochemical changes that characterize aging and the molecular processes that underlie these changes in humans have remained largely obscure. Recent advances have implicated several diverse processes in aging phenotypes in model organisms including oxidative damage, caloric intake, epigenetic regulation, hormonal signaling and telomere shortening. Likewise, aging phenotypes themselves are diverse, making it unlikely that all aging phenotypes are caused by any one stimulus. Many of these molecular causes of aging and pathways associated with aging may impinge upon tissue function as a common denominator. Many aging-related phenotypes share an underlying common impairment of proliferation or maintenance of self-renewing tissues. All these proliferative tissues are maintained by self-renewing stem cells, which has led some investigators to speculate that defects in aging stem cells may in turn underlie the impaired proliferative responses in many aging tissues. We are investigating the relationships between stem cell function and aging-related phenotypes using gene knockouts and transgenic approaches that modulate stem cell function. Using these genetic strategies, we seek to understand the relationship between stem cell reserve and aging.