Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Genes Dev. 2024 Oct 16;38(17-20):823-842. doi: 10.1101/gad.351728.124.
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.
成年多细胞生物中的细胞可塑性是一种保护机制，允许某些组织在受伤后再生。考虑到衰老涉及一生中反复暴露于损伤，细胞身份本身在年龄增长过程中可能更具可塑性，而且可能更容易出错。在这篇综述中，我们总结并批判性地讨论了现有的证据，证明细胞的身份随着年龄的增长而发生相关变化，重点讨论了那些导致与年龄相关的病理的变化，包括神经退行性变和癌症。具体来说，我们关注与去分化、偏向分化、获得来自其他谱系的特征以及进入癌前状态相关的程序的报道实例。由于一些据称能使细胞恢复活力的最有前途的方法也会引起细胞身份的短暂变化，我们进一步讨论了细胞状态的改变和恢复活力是否可以分离，以产生更易于治疗的策略。
