Mesenchymal drift: A convergent framework for the hallmarks of aging.

Aging is characterized by the loss of tissue homeostasis, traditionally captured by the telomere(definition) attrition, cellular senescence(definition))." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">hallmarks of aging(definition), yet how these hallmarks integrate to drive organismal decline remains unresolved. We propose mesenchymal drift, a process in which cells progressively lose lineage identity and adopt mesenchymal features, as a convergent framework that integrates the hallmarks of aging. Accumulating evidence suggests that mesenchymal drift can both arise from and reinforce these hallmarks, forming a feedback network that drives systemic decline. Framing aging through mesenchymal drift shifts the focus from discrete molecular defects to interconnected disruptions in cellular identity and cell state regulation, providing a more cohesive view of aging biology. Mesenchymal drift may therefore represent a measurable and targetable mechanism underlying diverse age-related pathologies. Interventions such as partial reprogramming(definition) may restrain mesenchymal drift, restore cellular identity, and simultaneously counteract multiple hallmarks, positioning it as both a convergent nexus and a tractable therapeutic axis in aging biology.