Scholarlink

<p>Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD<sup>+</sup> metabolism, supporting NAD<sup>+</sup> as a potential therapeutic target in aging. A gene encoding a cell-adhesion protein, PCDHGA1, emerged as a conserved hub across tissues, implicating cell-to-cell communication pathways in aging across multiple organs. Our methylation atlas therefore provides a resource for dissecting the molecular basis of human aging and for identifying potential biomarkers and translational therapies.</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

Meta-analysis of DNA methylation aging signatures in 17 human tissues

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月26日

查看全文
  • Macsue Jacques,
  • Kirsten Seale,
  • Sarah Voisin,
  • Anna Lysenko,
  • Robin Grolaux,
  • Bernadette Jones-Freeman,
  • Severine Lamon,
  • Mandhri Abeysooriya,
  • Itamar Levinger,
  • Carlie Bauer,
  • Adam P. Sharples,
  • Aino Heikkinen,
  • Elina Sillanpaa,
  • Miina Ollikainen,
  • Cassandra Smith,
  • James R. Broatch,
  • Navabeh Zarekookandeh,
  • Linn Gillberg,
  • Ida Blom,
  • Jesse R. Poganik,
  • Mahdi Moqri,
  • Vadim N. Gladyshev,
  • Matthew Taper,
  • Cassandra Malecki,
  • Sean Lal,
  • Nathalie Saurat,
  • Steve Horvath,
  • Andrew Teschendorff,
  • Nir Eynon

摘要

Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular disorder across tissues. Network analysis revealed tightly connected gene clusters that are not modified by beneficial interventions, alongside a more modifiable cluster linked to NAD+ metabolism, supporting NAD+ as a potential therapeutic target in aging. A gene encoding a cell-adhesion protein, PCDHGA1, emerged as a conserved hub across tissues, implicating cell-to-cell communication pathways in aging across multiple organs. Our methylation atlas therefore provides a resource for dissecting the molecular basis of human aging and for identifying potential biomarkers and translational therapies.