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Replicative senescence, induced by telomere shortening, exhibits considerableasynchrony and heterogeneity, the origins of which remain unclear. Here, weformally study how telomere shortening mechanisms impact on senescence kineticsand define two regimes of senescence, depending on the initial telomere lengthvariance. We provide analytical solutions to the model, highlighting anon-linear relationship between senescence onset and initial telomere lengthdistribution. This study reveals the complexity of the collective behavior oftelomeres as they shorten, leading to senescence heterogeneity.

Effects of initial telomere length distribution on senescence onset and heterogeneity