作者
Bohan Zhang, Andrei E Tarkhov, Wil Ratzan, Kejun Ying, Mahdi Moqri, Jesse R Poganik, Benjamin Barre, Alexandre Trapp, Joseph A Zoller, Amin Haghani, Steve Horvath, Leonid Peshkin, Vadim N Gladyshev
发表日期
2022/8/4
期刊
bioRxiv
页码范围
2022.08. 02.502559
出版商
Cold Spring Harbor Laboratory
简介
Recent studies suggest the existence of a natural rejuvenation event during early embryonic development of mice, followed by epigenetic aging. Here, by profiling embryonic DNA methylation in the African clawed frog, Xenopus laevis, we found that the epigenetic entropy basepoint maps to the gastrulation stage of embryogenesis and corresponds to a rapid increase in embryo transcript abundance. We further developed a frog aging clock, revealing that this species epigenetically ages. Application of this clock to developmental stages identified a decrease in epigenetic age during early embryogenesis, with the minimal age reached around gastrulation. By examining individual developmental trajectories of 6,457 embryos, we found that this stage is also accompanied by a higher incidence of disrupted development. Taken together, our data point to gastrulation as a critical stage for aging and natural rejuvenation, characterized by the lowest epigenetic age, increased mortality, nadir of DNA methylation entropy and rapid increase in embryo transcript abundance, defining aging ground zero as the basepoint where rejuvenation ends and the aging process begins.
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