Age-Related Changes in Tissue-Specific Stem Cells.

Aging of multicellular organisms typically involves progressive decline in the body’s ability to maintain homeostatic cell replacement and to regenerate tissues and organs after injury. In both the blood and the skeletal muscle, aging significantly impairs regenerative activity and can dysregulate normal homeostatic production of mature cells. These age-acquired defects in tissue function profoundly impact the health of older individuals, as evidenced by the high incidence of age-related muscle deterioration (sarcopenia), bone marrow failure, immune dysfunction, and blood cancers in the elderly. How aging causes deterioration of tissue function is poorly understood, but several lines of evidence suggest that loss or functional impairment of tissue-specific stem cells directly contributes to age-dependent failures in tissue repair. Interestingly, the effects of aging on tissue stem cell function appear to arise at least in part from alterations in the aged tissue environment, which can inhibit stem cell activity in older animals and may be regulated by factors that circulate naturally in the bloodstream. By making use of sensitive in vivo and in vitro approaches, including direct cell isolation by FACS, we are investigating the extrinsic factors and interactions that control stem cell function in aged animals. Our current studies have pointed us toward a discrete set of metabolic regulators and inflammatory cytokines, which may alter the signals that stem cells receive from their environment in aged animals. The knowledge we gain from these ongoing studies will help to define novel strategies to delay or reverse the onset of age-related disease, extending the healthful life of aging individuals.