Cellular Senescence and Stem Cell Exhaustion: Implications for Aging and Regeneration
摘要
Cellular senescence occurs when cells cease to divide in response to several internal and external stimuli, including stress and developmental cues. This process causes significant molecular and phenotypic changes and requires the dynamic and multi-step evolution of cellular properties. Even though they are still alive, senescent cells undergo changes in metabolism and gene expression, lose their ability to multiply, and become resistant to mitogenic signals. Senescence is a critical step in the aging and growth of organisms. Although it is typically marked by irreversible cell cycle arrest, cell cycle re-entry may be feasible in some cases, particularly in tumor cells. Even though stem cells are usually characterized as “immortal” since they do not undergo replicative senescence, they do sustain damage over time. The aging process has two effects on stem cells: it diminishes their quantity and changes the composition of subpopulations, affecting their ability to regenerate. Despite an overall loss in the stem cell pool, certain tissues exhibit an increase in adult stem cell populations as they age, whereas parent clones decrease. This implies that tissue homeostasis and regeneration are maintained via a compensatory mechanism in which fewer pluripotent stem cells produce more progeny. This chapter underlines the significance of these processes in aging and tissue regeneration by investigating the intricate relationship between stem cell dynamics and cellular senescence. Understanding the mechanisms underlying senescence and stem cell adaptation is crucial for developing strategies to enhance tissue repair and counteract the detrimental effects of aging.