bioRxivMolecular BiologyPreprint
Erosion of the Epigenetic Landscape and Loss of Cellular Identity as a Cause of Aging in Mammals
Jae-Hyun YangiD, Patrick T. GriffiniD, Daniel L. VeraiD, John K. Apostolides, Motoshi HayanoiD, Margarita V. MeeriD, Elias SalfatiiD, Qiao SuiD, Elizabeth M. Munding, Marco BlanchetteiD, Mital S. Bhakta, Zhixun DouiD, Caiyue XuiD, Jeffrey W. PippiniD, Michael L. CreswelliD, Brendan L. O’ConnelliD, Richard Edward GreeniD, Benjamin A. GarciaiD, Shelley L. BergeriD, Philipp OberdoerfferiD, Stuart J. ShanklandiD, Vadim N. GladysheviD, Luis A. RajmaniD, Andreas R. PfenningiD, David A. SinclairiD
Abstract
All living things experience entropy, manifested as a loss of inherited genetic and epigenetic information over time. As budding yeast cells age, epigenetic changes result in a loss of cell identity and sterility, both hallmarks of yeast aging. In mammals, epigenetic information is also lost over time, but what causes it to be lost and whether it is a cause or a consequence of aging is not known. Here we show that the transient induction of genomic instability, in the form of a low number of non-mutagenic DNA breaks, accelerates many of the chromatin and tissue changes seen during aging, including the erosion of the epigenetic landscape, a loss of cellular identity, advancement of the DNA methylation clock and cellular senescence. These data support a model in which a loss of epigenetic information is a cause of aging in mammals.\n\nOne Sentence SummaryThe act of repairing DNA breaks induces chromatin reorganization and a loss of cell identity that may contribute to mammalian aging
- organism: mouse
- assay: DNA methylation
- assay: ChIP-seq
- research focus: cell type annotation
- research focus: differential expression
- research focus: gene regulatory network inference
- research focus: cell-cell communication
- approach: experimental assay
- Citations
- 38
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- DNA Break-Induced Epigenetic Drift as a Cause of Mammalian Aging
Motoshi Hayano, Jae-Hyun Yang, … David A. Sinclair·bioRxiv·Oct 21, 2019
- An epigenetic landscape governs early fate decision in cellular aging
Yang Li, Yanfei Jiang, … Nan Hao·SciencePeer-reviewed·Jul 17, 2020
- Aging drives a program of DNA methylation decay in plant organs
Dawei Dai, Ken Chen, … Ben P. Williams·SciencePeer-reviewed·Jan 29, 2026
- Replicative history as a major determinant of epigenetic noise across human tissues
Alfonso Peñarroya, Juan José Alba‐Linares, … Juan Ramón Tejedor·bioRxiv·Aug 24, 2026
- A cross-species single-cell epigenome kidney atlas identifies epithelial cells as a driver of epigenetic aging
Hyeonsoo Jeong, Blue B. Lake, … Kun Zhang·bioRxiv·Jan 23, 2026
- FOXM1 enhances DNA repair in aged cells to maintain the peripheral heterochromatin barrier to senescence enhancers
Carlos Sousa-Soares, Marcos Antonio Barbosa Da Silva, … Elsa Logarinho·bioRxiv·Oct 29, 2025