4.7 Article

Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment

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NATURE NEUROSCIENCE
卷 25, 期 12, 页码 1714-+

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NATURE PORTFOLIO
DOI: 10.1038/s41593-022-01197-0

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资金

  1. National Institutes of Health [R01-MH118203, U01-MH121260, R01-MH096875, R01-AG060931, R00-AG051764, R01-NS097537, R35-GM124827, K99-AG075241, P40-OD012217]
  2. National Science Foundation [BCS-1800558, BCS-1752393]
  3. Brotman Baty Institute
  4. National Institutes of Health fellowship [T32-AG000057]
  5. Common Fund of the Office of the Director of the National Institutes of Health
  6. NCI
  7. NHGRI
  8. NHLBI
  9. NIDA
  10. NIMH
  11. NINDS - NCI\Leidos Biomedical Research, Inc. [10XS170]
  12. Roswell Park Cancer Institute [10XS171]
  13. Science Care, Inc. [X10S172, HHSN268201000029C]
  14. Leidos Biomedical Research, Inc. [10ST1035]
  15. Leidos Biomedical Research [HHSN261200800001E, DA006227, MH090941, MH101814]
  16. University of Chicago [MH090951, MH090937, MH101825, MH101820, MH090936]
  17. North Carolina State University [MH101819]
  18. Harvard University [MH090948]
  19. Stanford University [MH101782, MH101810, MH101822]
  20. Mayo Clinic Alzheimer's Disease Genetic Studies
  21. Mayo Clinic Alzheimer's Disease Research Center
  22. Mayo Clinic Brain Bank
  23. NIA [P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36042]
  24. NINDS [U24 NS072026]
  25. CurePSP Foundation
  26. Mayo Foundation
  27. Sun Health Research Institute Brain and Body Donation Program of Sun City, AZ
  28. (National Brain and Tissue Resource for Parkinson's Disease and Related Disorders)
  29. (Arizona Alzheimer's Disease Core Center)
  30. Arizona Department of Health Services [211002]
  31. Arizona Biomedical Research Commission [4001, 0011, 05-901, 1001]
  32. Michael J. Fox Foundation for Parkinson's Research
  33. Mount Sinai School of Medicine
  34. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL
  35. (ATACseq) [RC2AG036547, R01AG36836, R01AG48015, U01AG32984, U01AG46152, U01AG46161, U01AG61356]
  36. Illinois Department of Public Health (ROSMAP)

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This study provides insights into the biological mechanisms underlying brain aging in a nonhuman primate model of human behavior, cognition, and health. The researchers analyzed a multiregion bulk and single-nucleus brain transcriptional dataset from free-ranging rhesus macaques, and found age-related changes in gene expression associated with neural functions and neurological diseases. The study also revealed a link between higher social status in females and younger relative transcriptional ages.
Aging is accompanied by a host of social and biological changes that correlate with behavior, cognitive health and susceptibility to neurodegenerative disease. To understand trajectories of brain aging in a primate, we generated a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques. We demonstrate that age-related changes in the level and variance of gene expression occur in genes associated with neural functions and neurological diseases, including Alzheimer's disease. Further, we show that higher social status in females is associated with younger relative transcriptional ages, providing a link between the social environment and aging in the brain. Our findings lend insight into biological mechanisms underlying brain aging in a nonhuman primate model of human behavior, cognition and health. Chiou et al. provide a multiregion bulk (N = 527 samples) and single-nucleus (N = 24 samples) brain transcriptional dataset encompassing 15 brain regions and both sexes in a unique population of free-ranging, behaviorally phenotyped rhesus macaques.

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