作者
Patrick T Griffin, Alice E Kane, Alexandre Trapp, Jien Li, Matthew Arnold, Jesse R Poganik, Ryan J Conway, Maeve S McNamara, Margarita V Meer, Noah Hoffman, João A Amorim, Xiao Tian, Michael R MacArthur, Sarah J Mitchell, Amber L Mueller, Colleen Carmody, Daniel L Vera, Csaba Kerepesi, Kejun Ying, Nicole Noren Hooten, James R Mitchell, Michele K Evans, Vadim N Gladyshev, David A Sinclair
发表日期
2024/2
期刊
Nature Aging
卷号
4
期号
2
页码范围
261-274
出版商
Nature Publishing Group US
简介
Epigenetic ‘clocks’ based on DNA methylation have emerged as the most robust and widely used aging biomarkers, but conventional methods for applying them are expensive and laborious. Here we develop tagmentation-based indexing for methylation sequencing (TIME-seq), a highly multiplexed and scalable method for low-cost epigenetic clocks. Using TIME-seq, we applied multi-tissue and tissue-specific epigenetic clocks in over 1,800 mouse DNA samples from eight tissue and cell types. We show that TIME-seq clocks are accurate and robust, enriched for polycomb repressive complex 2-regulated loci, and benchmark favorably against conventional methods despite being up to 100-fold less expensive. Using dietary treatments and gene therapy, we find that TIME-seq clocks reflect diverse interventions in multiple tissues. Finally, we develop an economical human blood clock (R > 0.96, median error = 3 …
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