Journal
SCIENCE
Volume 359, Issue 6375, Pages 555-558Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao4426
Keywords
-
Categories
Funding
- Harvard/MIT MD-PHD program
- Stuart H. Q. and Victoria Quan Fellowship in Neurobiology
- Paul G. Allen Family Foundation
- [K99 AG054749 01]
- [F30 MH102909]
- [1S10RR028832-01]
- [T32HG002295]
- [U01MH106883]
- [P50MH106933]
- [R01 NS032457 U01 MH106883]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available