DNA methylation entropy as a measure of stem cell replication and aging

Genome Biology

Research

Jozef Madzo¹  Jaroslav Jelinek¹  Gennaro Calendo¹  Kelsey Keith¹  Jean-Pierre J. Issa¹  Himani Vaidya¹  Hye Seon Jeong²  Shinji Maegawa³ 

[1] Coriell Institute for Medical Research, 08013, Camden, NJ, USA;Coriell Institute for Medical Research, 08013, Camden, NJ, USA;Department of Neurology, Chungnam National University Hospital, Daejeon, South Korea;Department of Pediatrics, University of Texas, MD Anderson Cancer Center, Houston, TX, USA;

关键词: DNA methylation;    Aging;    Stem cell;    Cell division;    Epigenetic clock;   

DOI  :  10.1186/s13059-023-02866-4

 received in 2022-03-29, accepted in 2023-02-05,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundEpigenetic marks are encoded by DNA methylation and accumulate errors as organisms age. This drift correlates with lifespan, but the biology of how this occurs is still unexplained. We analyze DNA methylation with age in mouse intestinal stem cells and compare them to nonstem cells.ResultsAge-related changes in DNA methylation are identical in stem and nonstem cells, affect most prominently CpG islands and correlate weakly with gene expression. Age-related DNA methylation entropy, measured by the Jensen-Shannon Distribution, affects up to 25% of the detectable CpG sites and is a better measure of aging than individual CpG methylation. We analyze this entropy as a function of age in seven other tissues (heart, kidney, skeletal muscle, lung, liver, spleen, and blood) and it correlates strikingly with tissue-specific stem cell division rates. Thus, DNA methylation drift and increased entropy with age are primarily caused by and are sensors for, stem cell replication in adult tissues.ConclusionsThese data have implications for the mechanisms of tissue-specific functional declines with aging and for the development of DNA-methylation-based biological clocks.

【 授权许可】

CC BY   
© The Author(s) 2023

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