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.

中文翻译：

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穆勒的棘轮和老化。

衰老导致生理过程不可逆转的减速，代谢活动的改变以及组织，器官和器官系统完整性的下降。已经提出了遗传和表观遗传空间中变化的积累来解释衰老。它们至少部分是由于在发育，生长，更新和修复过程中由于细胞分裂引起的DNA复制和染色体分离错误。这种有害的变化，包括表观遗传漂移，不可逆地以逐步，棘轮状的方式积累，并降低了细胞的适应性，类似于穆勒棘轮的过程。在这里，我们回顾了应用于体细胞群体衰老的穆勒棘轮原理，并讨论了理解衰老，虚弱和发病原因的含义。