全面的DNA甲基化年龄在哺乳动物组织中的普遍存在。
Universal DNA methylation age across mammalian tissues.
发表日期：2023 Aug 10
作者：
A T Lu, Z Fei, A Haghani, T R Robeck, J A Zoller, C Z Li, R Lowe, Q Yan, J Zhang, H Vu, J Ablaeva, V A Acosta-Rodriguez, D M Adams, J Almunia, A Aloysius, R Ardehali, A Arneson, C S Baker, G Banks, K Belov, N C Bennett, P Black, D T Blumstein, E K Bors, C E Breeze, R T Brooke, J L Brown, G G Carter, A Caulton, J M Cavin, L Chakrabarti, I Chatzistamou, H Chen, K Cheng, P Chiavellini, O W Choi, S M Clarke, L N Cooper, M L Cossette, J Day, J DeYoung, S DiRocco, C Dold, E E Ehmke, C K Emmons, S Emmrich, E Erbay, C Erlacher-Reid, C G Faulkes, S H Ferguson, C J Finno, J E Flower, J M Gaillard, E Garde, L Gerber, V N Gladyshev, V Gorbunova, R G Goya, M J Grant, C B Green, E N Hales, M B Hanson, D W Hart, M Haulena, K Herrick, A N Hogan, C J Hogg, T A Hore, T Huang, J C Izpisua Belmonte, A J Jasinska, G Jones, E Jourdain, O Kashpur, H Katcher, E Katsumata, V Kaza, H Kiaris, M S Kobor, P Kordowitzki, W R Koski, M Krützen, S B Kwon, B Larison, S G Lee, M Lehmann, J F Lemaitre, A J Levine, C Li, X Li, A R Lim, D T S Lin, D M Lindemann, T J Little, N Macoretta, D Maddox, C O Matkin, J A Mattison, M McClure, J Mergl, J J Meudt, G A Montano, K Mozhui, J Munshi-South, A Naderi, M Nagy, P Narayan, P W Nathanielsz, N B Nguyen, C Niehrs, J K O'Brien, P O'Tierney Ginn, D T Odom, A G Ophir, S Osborn, E A Ostrander, K M Parsons, K C Paul, M Pellegrini, K J Peters, A B Pedersen, J L Petersen, D W Pietersen, G M Pinho, J Plassais, J R Poganik, N A Prado, P Reddy, B Rey, B R Ritz, J Robbins, M Rodriguez, J Russell, E Rydkina, L L Sailer, A B Salmon, A Sanghavi, K M Schachtschneider, D Schmitt, T Schmitt, L Schomacher, L B Schook, K E Sears, A W Seifert, A Seluanov, A B A Shafer, D Shanmuganayagam, A V Shindyapina, M Simmons, K Singh, I Sinha, J Slone, R G Snell, E Soltanmaohammadi, M L Spangler, M C Spriggs, L Staggs, N Stedman, K J Steinman, D T Stewart, V J Sugrue, B Szladovits, J S Takahashi, M Takasugi, E C Teeling, M J Thompson, B Van Bonn, S C Vernes, D Villar, H V Vinters, M C Wallingford, N Wang, R K Wayne, G S Wilkinson, C K Williams, R W Williams, X W Yang, M Yao, B G Young, B Zhang, Z Zhang, P Zhao, Y Zhao, W Zhou, J Zimmermann, J Ernst, K Raj, S Horvath
来源：
Epigenetics & Chromatin
摘要：
衰老，通常被认为是细胞随机损伤的结果，可以通过DNA甲基化剖析准确地估计，这是泛组织表观遗传钟的基础。在这里，我们展示了纵观哺乳动物的一致性表观遗传钟的发展，使用了来自我们的哺乳动物甲基化联盟的11,754个甲基化阵列，涵盖了185个哺乳动物物种的59个组织类型。这些预测模型能够高度准确地估计哺乳动物组织的年龄 (r > 0.96)。年龄偏差与人类死亡风险、小鼠体增主轴突变和限制热量摄入有相关性。我们确定了特定的胞嘧啶甲基化水平随多个物种的年龄变化而变化的位点。这些位点在聚合酶抑制剂复合物2结合位置上高度富集，并且靠近与哺乳动物发育、癌症、肥胖和长寿相关的基因。我们的发现提供了新的证据，表明衰老在所有哺乳动物中具有进化保守性，并与发育过程交织在一起。 ©2023年作者。
Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.© 2023. The Author(s).