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Toward understanding genomic instability, mitochondrial dysfunction and aging
Author(s) -
Fakouri Nima B.,
Hou Yujun,
Demarest Tyler G.,
Christiansen Louise S.,
Okur Mustafa N.,
Mohanty Joy G.,
Croteau Deborah L.,
Bohr Vilhelm A.
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14663
Subject(s) - genome instability , mitophagy , mitochondrion , biology , mitochondrial dna , dna damage , microbiology and biotechnology , oxidative stress , genetics , dna , apoptosis , gene , autophagy , biochemistry
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.