Museum of Comparative Zoology, Harvard University, Cambridge, MA 02138, USA; Institute of Aging Research, Albert Einstein College of Medicine, Bronx, NY 10460, USA.
Graduate University for Advanced Studies, Hayama, Kanagawa 240-0193, Japan.
Trends Genet. 2020 Jun;36(6):395-402. doi: 10.1016/j.tig.2020.02.004. Epub 2020 Mar 18.
Aging entails an irreversible deceleration of physiological processes, altered metabolic activities, and a decline of the integrity of tissues, organs, and organ systems. The accumulation of alterations in the genetic and epigenetic spaces has been proposed as an explanation for aging. They result, at least in part, from DNA replication and chromosome segregation errors due to cell division during development, growth, renewal, and repair. Such deleterious alterations, including epigenetic drift, irreversibly accumulate in a stepwise, ratchet-like manner and reduce cellular fitness, similar to the process known as Muller's ratchet. Here, we revisit the Muller's ratchet principle applied to the aging of somatic cell populations and discuss the implications for understanding the origins of senescence, frailty, and morbidity.
衰老是指生理过程不可逆减速、代谢活动改变、组织、器官和系统完整性下降。遗传和表观遗传空间的改变积累被认为是衰老的一个解释。它们至少部分是由于发育、生长、更新和修复过程中细胞分裂导致的 DNA 复制和染色体分离错误造成的。这种有害的改变，包括表观遗传漂移，以逐步、棘轮式的方式不可逆转地积累，降低细胞适应性，类似于 Muller 棘轮过程。在这里，我们重新审视了 Muller 棘轮原理在体细胞群衰老中的应用，并讨论了理解衰老、脆弱和发病机制起源的意义。
