Effects of initial telomere length distribution on senescence onset and heterogeneity

TL;DR

This paper investigates how the initial distribution of telomere lengths influences the timing and variability of cellular senescence, revealing complex behaviors and two distinct regimes based on initial heterogeneity.

Contribution

It provides analytical models linking initial telomere length variance to senescence dynamics, advancing understanding of heterogeneity in cellular aging.

Findings

Two regimes of senescence depending on initial telomere length variance

Non-linear relationship between telomere distribution and senescence onset

Analytical solutions describing telomere shortening effects

Abstract

Replicative senescence, induced by telomere shortening, exhibits considerable asynchrony and heterogeneity, the origins of which remain unclear. Here, we formally study how telomere shortening mechanisms impact on senescence kinetics and define two regimes of senescence, depending on the initial telomere length variance. We provide analytical solutions to the model, highlighting a non-linear relationship between senescence onset and initial telomere length distribution. This study reveals the complexity of the collective behavior of telomeres as they shorten, leading to senescence heterogeneity.