Specific subtle changes in regulation or activity of factors that maintain homeostasis and cell differentiation may play significant roles in mammalian aging. Drift resulting from reaching the end of an organism's developmental program might involve a specific ordered set of changes. Several studies have suggested that dysfunctional changes associated with aging in skeletal muscle, neurons, and hematopoietic stem cells may be caused by specific changes either in the extracellular environment or in intracellular regulatory networks and that such dysfunction may be reversible. On the basis these data, Loffredo et al. hypothesized that extrinsic circulating factors in young mice might reverse cardiac aging. Parabiosis, the surgical linking of circulations between old and young mice, was employed to identify an anti-hypertrophic factor (growth differentiation factor 11 [GDF-11]) that appears to rejuvenate aging murine hearts, raising exciting prospects for the development of anti-aging therapeutics. However, much work remains to be done to evaluate the utility of GDF-11 as a therapeutic rejuvenation factor. Similar rejuvenating factors for diverse tissues may exist as well and will hopefully be identified in the near future.