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While DNA damage and subsequent mutation in somatic cells were first proposed as drivers of aging more than 60\u00a0years ago, whether and to what degree these processes shape the neuronal genome in the human brain could not be tested until recent technological breakthroughs related to single-cell whole-genome sequencing. Indeed, somatic single-nucleotide variants (SNVs) increase with age in the human brain, in a somewhat stochastic process that may nonetheless be controlled by underlying genetic programs. Evidence from the literature suggests that in addition to demonstrated increases in somatic SNVs during aging in normal brains, somatic mutation may also play a role in late-onset, sporadic neurodegenerative diseases, such as Alzheimer\u2019s disease and Parkinson\u2019s disease. In this review, we will discuss somatic mutation in the human brain, mechanisms by which somatic mutations occur and can be controlled, and how this process can impact human health.<\/jats:p>","DOI":"10.1093\/hmg\/ddz191","type":"journal-article","created":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T03:52:32Z","timestamp":1570074752000},"page":"R197-R206","source":"Crossref","is-referenced-by-count":53,"title":["Genome aging: somatic mutation in the brain links age-related decline with disease and nominates pathogenic mechanisms"],"prefix":"10.1093","volume":"28","author":[{"given":"Michael A","family":"Lodato","sequence":"first","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease, Boston Children\u2019s Hospital, Boston, MA, USA"},{"name":"Howard Hughes Medical Institute, Boston, MA, USA"},{"name":"Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA"},{"name":"Department of Molecular, Cell, and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A","family":"Walsh","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease, Boston Children\u2019s Hospital, Boston, MA, USA"},{"name":"Howard Hughes Medical Institute, Boston, MA, USA"},{"name":"Departments of Neurology and Pediatrics, Harvard Medical School, Boston, MA, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,6]]},"reference":[{"key":"2019112809503360600_ref1","first-page":"10083","article-title":"The current state of eukaryotic DNA base damage and repair","volume":"43","author":"Bauer","year":"2015","journal-title":"Nucleic Acids 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