Stem cell aging.

202 W E summarize here the fruitful discussion that occurred on a wide variety of topics during the session on stem cell aging. Somatic Stem Cell Aging Do stem cells age; and if they do, how can these changes be reliably identifi ed? Most attendees were of the view that a decline in the function of tissue-specifi c somatic stem cells is likely to play an important role in human aging. Results from several mammalian systems were discussed including stem cells of the adult bone marrow, brain, intestine, and muscle. Also, there was a brief discussion of what should constitute a stem cell for the purposes of this discussion, for example, cells like pancreatic b cells, muscle stem cells, and memory T cells appear to share some important features with more classically defi ned stem cells (eg, an ability to self-renew in adult organisms), but which lack the capacity for broad multilineage differentiation thought to be the sine qua non of a " true " stem cell. Although some aspects of mammalian aging may be shared among such long-term, self-renewing cells with aging, a consensus view emerged that the mechanism and functional consequences of aging are likely to differ markedly by tissue and cell type. For example, transplantable and cell-intrinsic defects and he-matopoietic stem cell (HSC) function have been identifi ed by several investigators (1 , 2), and these defects seem to be increased by stimuli that attenuate DNA repair. In contrast, work of Conboy and colleagues (3) suggests that significant aspects of muscle stem cell aging are cell extrinsic and rather refl ect changes in the stem cell milieu (or " niche " ; see following). Potential causes of cell-intrinsic aging were discussed. The role of tumor suppressor induction (p53 (4) and p16 INK4a (5 , 6)) in response to cumulative DNA damage, telomere dysfunction, and other stresses were considered important. These alterations may in turn refl ect changes in stem cell chromatin structure, for example, the role of Polycomb group proteins in regulating the INK4A/ARF locus was discussed as a potential contributor to stem cell aging (7). Along these lines, several of the discussants indicated that studies of epigenetic changes, presumably using both candidate approaches and epigenome-wide genomic approaches, should be priorities for future study (see also article by Kahn & Fraga, [ 8 ]). Also, an enhanced understanding of stem cell aging was identifi ed as a …