Longevity Pathways in Mammalian Stem Cells

Aging is accompanied by a general decline in tissue function and a striking increase in diseases. With their ability to self-renew and differentiate, adult stem cells represent a regenerative reserve for the aging tissue. Understanding the mechanisms underlying the age-dependent decline in adult stem cell function should help identify ways to preserve tissue homeostasis during aging. Tapping into the potential of adult stem cells should also allow tissue repair and regeneration in the case of degenerative diseases linked with age. In contrast to adult stem cells, embryonic stem cells have unlimited self-renewal and pluripotency, and the mechanisms underlying their "immortality" may give clues into fundamental principles governing cellular youth or rejuvenation. The advent of cellular reprogramming, which allows the generation of patient-specifi c pluripotent stem cells, has opened new avenues for therapeutic treatments of age-related diseases. This chapter reviews how longevity pathways infl uence stem cell function in mammalian adult stem cells, embryonic stem cells, and induced pluripotent stem cells. We specifi cally discuss genetic pathways that play a conserved role in lifespan, such as the insulin-FOXO pathway and the mechanistic target of rapamycin (mTOR) pathway, as well as metabolic enzymes that are involved in health span, such as AMP-activated protein kinase (AMPK) and Sirtuins.