Changes in cell signaling pathways of tissue-specific stem cells have been implicated in the decreased capacity for regeneration that accompanies aging. For instance, diminished Notch signaling in muscle stem cells (known as satellite cells) is associated with impaired regeneration of aged muscle, whereas a shift in the pathway through which the transcription factor cEBP-α inhibits cell proliferation is involved in the loss of regenerative capacity of aged liver. Conboy et al. established pairs of mice with shared circulatory systems to see whether circulating factors found in young animals could affect the regenerative capacity of aged progenitor cells. Pairing aged (19 to 26 months old) mice with young ones (2 to 3 months old) promoted muscle regeneration from the satellite cells of the aged mice following injury. Satellite cells in explants from these mice showed increased expression of the Notch ligand, Delta. Delta expression was also increased in satellite cells from old mice that were cultured in the presence of serum from young mice, as were Notch activation and cell proliferation. Hepatocyte proliferation was enhanced in aged mice paired with young ones, whereas formation of a complex between cEBP-α and the chromatin remodeling factor brahma, which is associated with the aging-related loss of hepatocyte proliferative capacity, was decreased. Thus, the authors conclude that systemic factors circulating in young animals have the capacity to modulate the signaling pathways required for activation of tissue-specific stem cells and thereby enhance the regenerative capacity of aged tissue.
I. M. Conboy, M. J. Conboy, A. J. Wagers, E. R. Girma, I. L. Weissman, T. A. Rando, Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433, 760-764 (2005). [PubMed]