Senescent cells and the dynamics of aging

Abstract

Genetically-identical organisms age at different rates, but the reason for this is unclear. The rate of aging is due to the accumulation of damage, such as senescent cells (SnC) which are a major driver of aging in mammals, but the accumulation dynamics of SnC are unknown. Here, we combine theory and experiments in mice and find that SnC are rapidly produced and removed with a half-life of days in young mice. In old mice SnC half-life grows to weeks, because SnC saturate their own removal process. This saturation leads to persistent fluctuations known as critical-slowing-down: fluctuations are amplified to long-lasting differences in SnC between individuals at old ages. Rapid turnover with saturating removal is a general framework that may apply to any aging-related form of damage, and can quantitatively explain the demographic laws of mortality in worms, flies, mice and humans.