MINI REVIEW article
Front. Pharmacol.
Sec. Pharmacogenetics and Pharmacogenomics
This article is part of the Research TopicAdvancements in Pharmacological Epigenetics for Aging and Age-related DiseasesView all 5 articles
Inhibition of mesenchymal drift as a strategy for rejuvenation
Provisionally accepted
- 1School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
- 2Shift Bioscience Ltd, Cambridge, United Kingdom
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Mesenchymal drift (MD), the progressive acquisition of mesenchymal traits by epithelial and endothelial cells, has emerged as a unifying mechanism of aging. Transcriptomic analyses across human tissues reveal that mesenchymal programs intensify with age and predict morbidity and mortality. By eroding lineage identity and promoting fibrosis, MD disrupts organ integrity in the lung, liver, kidney, heart, and brain. Mechanistically, it converges with epigenetic erosion, chronic inflammation, and extracellular matrix stiffening to establish self-reinforcing loops of dysfunction. Interventions that restore cellular identity can suppress MD: transient reprogramming resets epigenetic age and reduces fibrotic signatures without loss of identity, while chemical cocktails achieve similar rejuvenation effects with enhanced translational potential. Together, these findings establish MD as a tentative hallmark of aging and suggest that its inhibition could represent a strategy for cellular and tissue rejuvenation.
Keywords: Aging, Rejuvenation, EMT, reprogramming, OSKM
Received: 29 Sep 2025; Accepted: 28 Oct 2025.
Copyright: © 2025 De Lima Camillo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lucas Paulo De Lima Camillo, lucas_camillo@alumni.brown.edu
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