Telomeres, oxidative stress and inflammatory factors: partners in cellular senescence?

Abstract

Senescence, the state of irreversible cell-cycle arrest, plays paradoxical albeit important roles in vivo: it protects organisms against cancer but also contributes to age-related loss of tissue function. The DNA damage response (DDR) has a central role in cellular senescence. Not only does it contribute to the irreversible loss of replicative capacity but also to the production and secretion of reactive oxygen species (ROS), and bioactive peptides collectively known as the senescence-associated secretory phenotype (SASP). Both ROS and the SASP have been shown to impact on senescence in an autocrine as well as paracrine fashion; however, the underlying mechanisms are not well understood. In this review we describe our current understanding of cellular senescence, examine in detail the intricate pathways linking the DDR, ROS and SASP, and evaluate their impact on the stability of the senescent phenotype.