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Do DNA Double-Strand Breaks Drive Aging?
- Source :
-
Molecular cell [Mol Cell] 2016 Sep 01; Vol. 63 (5), pp. 729-38. - Publication Year :
- 2016
-
Abstract
- DNA double-strand breaks (DSBs) are rare, but highly toxic, lesions requiring orchestrated and conserved machinery to prevent adverse consequences, such as cell death and cancer-causing genome structural mutations. DSBs trigger the DNA damage response (DDR) that directs a cell to repair the break, undergo apoptosis, or become senescent. There is increasing evidence that the various endpoints of DSB processing by different cells and tissues are part of the aging phenotype, with each stage of the DDR associated with specific aging pathologies. In this Perspective, we discuss the possibility that DSBs are major drivers of intrinsic aging, highlighting the dynamics of spontaneous DSBs in relation to aging, the distinct age-related pathologies induced by DSBs, and the segmental progeroid phenotypes in humans and mice with genetic defects in DSB repair. A model is presented as to how DSBs could drive some of the basic mechanisms underlying age-related functional decline and death.<br /> (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Subjects :
- Acid Anhydride Hydrolases
Aging metabolism
Aging pathology
Animals
BRCA1 Protein genetics
BRCA1 Protein metabolism
Cell Cycle Proteins genetics
Cell Cycle Proteins metabolism
Cellular Senescence
DNA metabolism
DNA Repair Enzymes genetics
DNA Repair Enzymes metabolism
DNA-Binding Proteins genetics
DNA-Binding Proteins metabolism
Endonucleases genetics
Endonucleases metabolism
Humans
Ku Autoantigen genetics
Ku Autoantigen metabolism
MRE11 Homologue Protein
Mice
Models, Genetic
Nuclear Proteins genetics
Nuclear Proteins metabolism
Progeria metabolism
Progeria pathology
Saccharomyces cerevisiae genetics
Saccharomyces cerevisiae metabolism
Signal Transduction
Aging genetics
DNA genetics
DNA Breaks, Double-Stranded
DNA Repair
Gene Expression Regulation
Progeria genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 63
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 27588601
- Full Text :
- https://doi.org/10.1016/j.molcel.2016.08.004