Cellular plasticity in adult multicellular organisms is a protective mechanism that allows certain tissues to regenerate in response to injury. Considering that aging involves exposure to repeated injuries over a lifetime, it is conceivable that cell identity itself is more malleable—and potentially erroneous—with age. In this review, we summarize and critically discuss the available evidence that cells undergo age-related shifts in identity, with an emphasis on those that contribute to age-associated pathologies, including neurodegeneration and cancer. Specifically, we focus on reported instances of programs associated with dedifferentiation, biased differentiation, acquisition of features from alternative lineages, and entry into a preneoplastic state. As some of the most promising approaches to rejuvenate cells reportedly also elicit transient changes to cell identity, we further discuss whether cell state change and rejuvenation can be uncoupled to yield more tractable therapeutic strategies.

中文翻译：

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细胞身份危机？衰老和年轻化过程中的可塑性变化


成体多细胞生物的细胞可塑性是一种保护机制，允许某些组织响应损伤而再生。考虑到衰老涉及一生中反复受伤，可以想象，细胞身份本身会随着年龄的增长而更具延展性，并且可能具有错误性。在这篇综述中，我们总结并批判性地讨论了细胞经历与年龄相关的身份转变的现有证据，重点是那些导致与年龄相关的病理学（包括神经退行性和癌症）的证据。具体来说，我们专注于与去分化、偏倚分化、从替代谱系获得特征和进入癌前状态相关的程序的报道实例。据报道，由于一些最有前途的细胞恢复活力的方法也会引起细胞身份的瞬时变化，因此我们进一步讨论了细胞状态变化和恢复活力是否可以解耦以产生更易处理的治疗策略。