Abstract
Age-related and cancer-related epigenomic modifications have been associated with enhanced cell-to-cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by-and epigenetic and phenotypic stability acquired through-direct or long-range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell-cell interactions. Tissue-disruption-induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because of an increase in phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis.