Aging is a complex phenomenon, where damage accumulation, increasing deregulation of biological pathways, and loss of cellular homeostasis lead to the decline of organismal functions over time. Interestingly, aging is not entirely a stochastic process and progressing at a constant rate, but it is subject to extensive regulation, in the hands of an elaborate and highly interconnected signaling network. This network can integrate a variety of aging-regulatory stimuli, i.e. fertility, nutrient availability, or diverse stresses, and relay them via signaling cascades into gene regulatory events - mostly of genes that confer stress resistance and thus help protect from damage accumulation and homeostasis loss. Transcription factors have long been perceived as the pivotal nodes in this network. Yet, it is well known that the epigenome substantially influences eukaryotic gene regulation, too. A growing body of work has recently underscored the importance of the epigenome also during aging, where it not only undergoes drastic age-dependent changes but also actively influences the aging process. In this review, we introduce the major signaling pathways that regulate age-related decline and discuss the synergy between transcriptional regulation and the epigenetic landscape.

中文翻译：

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转录因子及其与表观基因组串扰对年龄相关衰退的调节


衰老是一种复杂的现象，随着时间的推移，损伤的积累、生物途径的失调以及细胞稳态的丧失会导致机体功能的衰退。有趣的是，衰老并不完全是一个随机过程，并且以恒定的速度进行，但它受到复杂且高度互连的信号网络的广泛调节。该网络可以整合各种衰老调节刺激，即生育力、营养可用性或不同的压力，并通过信号级联将它们传递到基因调节事件中——大多数基因赋予压力抵抗力，从而有助于防止损伤积累和体内平衡丧失。转录因子长期以来被认为是该网络中的关键节点。然而，众所周知，表观基因组也极大地影响真核基因调控。最近越来越多的工作强调了表观基因组在衰老过程中的重要性，它不仅经历了与年龄相关的剧烈变化，而且还积极影响衰老过程。在这篇综述中，我们介绍了调节与年龄相关的衰退的主要信号通路，并讨论了转录调控与表观遗传景观之间的协同作用。