Scholarlink

<p>DNA methylation changes are reliable biomarkers of aging, but the driving mechanisms remain poorly understood. Here we present SCARLET (Stem Cells and Age-ReLated Epigenetic Trajectories), a parsimonious mathematical model that describes how methylation changes in blood arise and propagate through hematopoietic stem cell divisions. Using a large human cohort, we demonstrate that seemingly distinct age-related methylation patterns can be explained by a unifying mechanistic model. We show that SCARLET captures known drivers of epigenetic aging, with accelerated individuals showing reduced ratios of stem cell pool size to division rate (<i>N</i>/<i>s</i>). Applying SCARLET to methylation data from 11 mammalian species reveals that <i>N</i>/<i>s</i> scales with maximum lifespan, suggesting that evolutionary adjustments to stem cell dynamics, rather than epigenetic maintenance efficiency, drive the previously observed relationship between methylation rates and lifespan. Our findings provide a quantitative framework for understanding epigenetic aging and suggest that stem cell dynamics may be a key driver of aging across mammals.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A unifying model of stem cell dynamics explains age-related methylation patterns across mammals

  • 期刊论文

  • 发表日期：

    2026年5月19日

查看全文
  • Samuel J. C. Crofts,
  • Caleb M. Grenko,
  • Riccardo E. Marioni,
  • Eric Latorre-Crespo,
  • Tamir Chandra

摘要

DNA methylation changes are reliable biomarkers of aging, but the driving mechanisms remain poorly understood. Here we present SCARLET (Stem Cells and Age-ReLated Epigenetic Trajectories), a parsimonious mathematical model that describes how methylation changes in blood arise and propagate through hematopoietic stem cell divisions. Using a large human cohort, we demonstrate that seemingly distinct age-related methylation patterns can be explained by a unifying mechanistic model. We show that SCARLET captures known drivers of epigenetic aging, with accelerated individuals showing reduced ratios of stem cell pool size to division rate (N/s). Applying SCARLET to methylation data from 11 mammalian species reveals that N/s scales with maximum lifespan, suggesting that evolutionary adjustments to stem cell dynamics, rather than epigenetic maintenance efficiency, drive the previously observed relationship between methylation rates and lifespan. Our findings provide a quantitative framework for understanding epigenetic aging and suggest that stem cell dynamics may be a key driver of aging across mammals.