Sikder Sweta, Arunkumar Ganesan, Melters Daniël P, Dalal Yamini
Chromatin Structure and Epigenetic Mechanisms, Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, NCI, NIH, Bethesda, MD, United States.
Front Cell Dev Biol. 2022 Jul 28;10:943519. doi: 10.3389/fcell.2022.943519. eCollection 2022.
Aging is an inexorable event occurring universally for all organisms characterized by the progressive loss of cell function. However, less is known about the key events occurring inside the nucleus in the process of aging. The advent of chromosome capture techniques and extensive modern sequencing technologies have illuminated a rather dynamic structure of chromatin inside the nucleus. As cells advance along their life cycle, chromatin condensation states alter which leads to a different epigenetic landscape, correlated with modified gene expression. The exact factors mediating these changes in the chromatin structure and function remain elusive in the context of aging cells. The accumulation of DNA damage, reactive oxygen species and loss of genomic integrity as cells cease to divide can contribute to a tumor stimulating environment. In this review, we focus on genomic and epigenomic changes occurring in an aged cell which can contribute to age-related tumor formation.
衰老是所有生物体普遍发生的不可避免的过程，其特征是细胞功能逐渐丧失。然而，关于衰老过程中细胞核内发生的关键事件，我们了解得较少。染色体捕获技术和广泛的现代测序技术的出现，揭示了细胞核内染色质相当动态的结构。随着细胞沿着其生命周期推进，染色质凝聚状态会发生改变，这会导致不同的表观遗传格局，与基因表达的改变相关。在衰老细胞的背景下，介导染色质结构和功能这些变化的确切因素仍然难以捉摸。随着细胞停止分裂，DNA损伤、活性氧的积累以及基因组完整性的丧失会促成肿瘤刺激环境。在本综述中，我们关注衰老细胞中发生的基因组和表观基因组变化，这些变化可能导致与年龄相关的肿瘤形成。
