Mesenchymal drift: A convergent framework for the hallmarks of aging

May 28, 2026Cell

Movement of Support Cells as a Common Factor in Aging Signs

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Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Mesenchymal drift may represent a measurable mechanism underlying diverse age-related pathologies.

Aging is linked to the loss of tissue homeostasis, traditionally understood through distinct hallmarks.
Mesenchymal drift involves cells losing their original identity and acquiring characteristics typical of mesenchymal cells.
This process can arise from and reinforce the hallmarks of aging, creating a feedback network that contributes to systemic decline.
Viewing aging through the lens of mesenchymal drift highlights the interconnected nature of cellular identity and regulatory disruptions.
Interventions like partial reprogramming could potentially restrain mesenchymal drift and restore cellular identity, addressing multiple hallmarks simultaneously.

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Aging is characterized by the loss of tissue homeostasis, traditionally captured by the hallmarks of aging, 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 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.