Aging and neurodegeneration are associated with increased mutations in single human neurons

• DOI: 10.1126/science.aao4426
• Publication Date: 2017-12-07T19:05:30Z
• Authors: Michael A. Lodato; Rachel E. Rodin; Craig L. Bohrson; Michael E. Coulter; Alison R. Barton; Minseok Kwon; Maxwell A. Sherman; Carl M. Vitzthum; Lovelace J. Luquette; Chandri N. Yandava; Pengwei Yang; Thomas W. Chittenden; Nicole E. Hatem; Steven C. Ryu; Mollie B. Woodworth; Peter J. Park; Christopher A. Walsh
• Keywords: Cockayne syndrome

It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide single-nucleotide variant (sSNV) identification on DNA from 161 single neurons the prefrontal cortex hippocampus of 15 normal individuals (aged 4 months 82 years), as well 9 affected by early-onset due genetic disorders repair (Cockayne syndrome xeroderma pigmentosum). sSNVs increased approximately linearly age both areas (with a higher rate hippocampus) were more abundant neurodegenerative disease. The accumulation mutations age-which we term genosenium-shows age-related, region-related, disease-related molecular signatures may be important other human age-associated conditions.