The many types of heterogeneity in replicative senescence

Abstract

Replicative senescence, which is induced by telomere shortening, underlies the loss of regeneration capacity of organs and is ultimately detrimental to the organism. At the same time, it is required to protect organisms from unlimited cell proliferation that may arise from numerous stimuli or deregulations. One important feature of replicative senescence is its high level of heterogeneity and asynchrony, which promote genome instability and senescence escape. Characterizing this heterogeneity and investigating its sources are thus critical to understanding the robustness of replicative senescence. Here we review the different aspects of senescence driven by telomere attrition that are subject to variation in Saccharomyces cerevisiae , the current understanding of the molecular processes at play, and the consequences of heterogeneity in replicative senescence.

Abstract

Here, we review the different facets of replicative senescence triggered by telomere erosion that are subject to variation in Saccharomyces cerevisiae. We decompose the molecular pathways involved in the generation of heterogeneity and discuss the consequences, in particular, as a threat to replicative senescence robustness. Many concepts discussed here likely apply to other eukaryotic cells in which telomerase is repressed physiologically.