Citation:
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, and Christopher A Walsh. 2018. “
Aging and neurodegeneration are associated with increased mutations in single human neurons.” Science, 359, 6375, Pp. 555-559.
Abstract:
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 somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age-which we term genosenium-shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.
