DNA损伤应答（DDR）是维持活体细胞稳态的关键生物学机制。这一复杂过程涉及一系列信号通路级联，用于协调DNA损伤的感知与修复过程。这一过程的干扰可能导致DNA修复失败、基因组不稳定性和不可逆的细胞周期停滞，即细胞衰老，最终可能导致肿瘤发生。持续的DDR对全局染色质动力学施加持续和累积的压力，导致染色质结构改变和干扰表观遗传调控，这与细胞衰老和衰老有关。持续的DDR激活和异染色质变化进一步促进了衰老相关分泌表型（SASP），这是衰老相关疾病和癌症发展的根源。在本综述中，我们讨论DDR导致细胞衰老和激活SASP的多种机制，以及与衰老相关的DDR引起的染色质重塑和表观遗传调控的证据。版权所有©2023作者。Elsevier B.V.发表, 版权所有。

The DNA damage response (DDR) is a crucial biological mechanism for maintaining cellular homeostasis in living organisms. This complex process involves a cascade of signaling pathways that orchestrate the sensing and processing of DNA lesions. Perturbations in this process may cause DNA repair failure, genomic instability, and irreversible cell cycle arrest, known as cellular senescence, potentially culminating in tumorigenesis. Persistent DDR exerts continuous and cumulative pressure on global chromatin dynamics, resulting in altered chromatin structure and perturbed epigenetic regulations, which are highly associated with cellular senescence and aging. Sustained DDR activation and heterochromatin changes further promote senescence-associated secretory phenotype (SASP), which is responsible for aging-related diseases and cancer development. In this review, we discuss the diverse mechanisms by which DDR leads to cellular senescence and triggers SASP, together with the evidence for DDR-induced chromatin remodeling and epigenetic regulation in relation to aging.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.