The Role of Stem Cell Genomic Instability in Aging

Abstract

Organismal aging is characterized by a progressive loss of tissue homeostasis and impaired function over time. Multi-cellular organisms activate stem and progenitor cells to replace damaged cells in order to continuously meet the functional demands of tissues. Along with tissue dysfunction, stem cell self-renewal and differentiation capacities diminish with age in concert with the accumulation of genomic damage, suggesting a potential link between genetic instability and aging. Here, we focus on the types of DNA damage found in aged stem cells, and discuss emerging mechanisms by which genomic instability may contribute to stem cell impairments and organismal aging, with particular emphasis on insights obtained from progeroid mouse models. Additionally, we discuss how age-related systemic changes may impact stem cell genomic integrity and function.