Toward understanding genomic instability, mitochondrial dysfunction and aging

作者：Nima Borhan Fakouri, Yujun Hou, Tyler G. Demarest, Louise Slot Christiansen, Mustafa Nazir Okur, Joy G. Mohanty, Deborah L. Croteau, Vilhelm A. Bohr · 发表于：FEBS Journal · 年份：2018 · DOI：10.1111/febs.14663 · 被引用次数：79 · 研究领域：DNA Repair Mechanisms、Mitochondrial Function and Pathology、Autophagy in Disease and Therapy

The biology of aging is an area of intense research, and many questions remain about how and why cell and organismal functions decline over time. In mammalian cells, genomic instability and mitochondrial dysfunction are thought to be among the primary drivers of cellular aging. This review focuses on the interrelationship between genomic instability and mitochondrial dysfunction in mammalian cells and its relevance to age-related functional decline at the molecular and cellular level. The importance of oxidative stress and key DNA damage response pathways in cellular aging is discussed, with a special focus on poly (ADP-ribose) polymerase 1, whose persistent activation depletes cellular energy reserves, leading to mitochondrial dysfunction, loss of energy homeostasis, and altered cellular metabolism. Elucidation of the relationship between genomic instability, mitochondrial dysfunction, and the signaling pathways that connect these pathways/processes are keys to the future of research on human aging. An important component of mitochondrial health preservation is mitophagy, and this and other areas that are particularly ripe for future investigation will be discussed.