10 Aging in Mammalian Stem Cells and Other Self-renewing Compartments

Long-lived metazoans must replace a variety of lost or consumed cells at a furious pace. For example, an adult human replaces about 1% of their 20 trillion red blood cells every day through de novo synthesis. Similarly staggering rates of cell division are at work to produce new cells in the gut, skin, and bone marrow throughout life. Additionally, certain tissues (e.g., memory lymphocytes and pancreatic β cells) possess a potential for facultative growth in the adult organism; i.e., under certain circumstances (e.g., viral infection and pregnancy), these normally quiescent cells can reenter the cell cycle to increase the mass of a given tissue through regulated proliferation. To offset the high cellular turnover rate in such tissues and avoid the onset of tissue-specific hypoplasia and atrophy, many mammalian tissues contain reservoirs of stem cells capable of generating terminally differentiated effector cell types. The unique cellular property that enables stem cells to maintain such function throughout is their ability to produce large numbers of differentiated cell types while also self-renewing themselves so that their reserves do not become depleted over time. Several lines of evidence—foremost of which is evidence indicating that aged tissues characteristically exhibit a diminished capacity to maintain homeostasis or return to homeostasis after exposure to stress—has implicated stem cell decline in the aging process. In this chapter, we review some of the evidence to support the notion that certain aspects of mammalian aging result from an age-dependent decline in the function of self-renewing stem cells, and...