STEM CELLS AND AGING: A GENETIC APPROACH
Gary Van Zant, PhD
Departments of Medicine and Physiology
University of Kentucky Medical Center
Lexington, KY 40536-0093
Self-renewing tissues rely on stem cell populations to continuously supply those mature cells with inherently short lifespans or those lost through wear and tear, disease, or accident. Stem cells must therefore function throughout the lifespan of an animal; failure to do so would result in life-threatening aplasias. Since stem cells are capable of not only supplying differentiated cells to a tissue, but also replicating to resupply their own numbers, it would seem that such populations would be exempt from age-related depletion. An alternative perspective is that they may be exquisitely sensitive to age-related functional decline if their regenerative properties are not fully maintained. Using lympho-hematopoiesis as a model, it is widely recognized that production of most blood cells is maintained at near-normal levels throughout the lifespans of rodents and humans. An exception is the redistribution in lymphoid cell subpopulations during aging resulting in the contraction of some subsets, and, of course, the involution of the thymus. It is further regognized that the response to hematological and immunological stress is blunted in older animals and humans despite the fact that in mice the number of stem cells actually increases in the bone marrow during normal aging. However, a growing body of evidence shows that despite an age-related increase in at least hematopoietic stem cell numbers, some functional capabilities of stem cells are compromised during aging. We discuss our recent studies using a genetic approach in mice to identify loci regulating stem cell populations during the aging process. Our data point to the notion that an age-related decline in stem cell function, perhaps due to replicative stress, directly affects organismal longevity.
Problems or questions regarding this site should be directed to
webmaster@americanaging.org