Adult Stem Cells and Diseases of Aging.
Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; lbb21@pitt.edu ; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Lisa B
LB
Boyette
Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA 15219, USA; lbb21@pitt.edu ; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA ; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Rocky S
RS
Tuan
FoxO; Wnt; aging; longevity; metabolic disease; oxidative stress; progeria; reprogramming; stem cells