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Cell Senescence and Cerebral Small Vessel Disease in the Brains of People Aged 80 Years and Older.
- Source :
-
Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2019 Nov 01; Vol. 78 (11), pp. 1066-1072. - Publication Year :
- 2019
-
Abstract
- Cerebral small vessel disease (cSVD) in penetrating arteries is a major cause of age-related morbidity. Cellular senescence is a molecular process targeted by novel senolytic drugs. We quantified senescence in penetrating arteries and tested whether myocyte senescence was associated with cSVD. We immunolabeled subcortical white matter of older persons (age 80-96 years, n = 60) with minimal AD, using antibodies to 2 established senescence markers (H3K9me3, γH2AX) and a myocyte marker (hSMM). Within the walls of penetrating arteries (20-300 µm), we quantified senescence-associated heterochromatic foci (SAHF)-positive nuclei, cell density (nuclei/µm2), and sclerotic index (SI). Senescent-appearing mural cells were present in small arteries of all cases. cSVD cases exhibited a lower proportion of senescent-appearing cells and lower area fraction (AF%) of SAHF-positive nuclei compared to controls (p = 0.014, 0.016, respectively). cSVD severity and SI both correlated negatively with AF% (p = 0.013, 0.002, respectively). Mural cell density was lower (p < 0.001) and SI higher (p < 0.001) in cSVD, relative to controls. In conclusion, senescent myocyte-like cells were universal in penetrating arteries of an AD-free cohort aged 80 years and older. Senescent-appearing nuclei were more common in persons aged 80 years and older without cSVD compared to cSVD cases, indicating caution in senolytic drug prescribing. Myocyte senescence and cSVD may represent alternative vessel fates in the aging human brain.<br /> (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)
- Subjects :
- Aged, 80 and over
Aging pathology
Aging physiology
Cerebral Arteries pathology
Cerebral Arteries physiopathology
Female
Humans
Male
White Matter pathology
White Matter physiopathology
Brain physiology
Brain physiopathology
Cellular Senescence
Cerebral Small Vessel Diseases pathology
Cerebral Small Vessel Diseases physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1554-6578
- Volume :
- 78
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Journal of neuropathology and experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 31553444
- Full Text :
- https://doi.org/10.1093/jnen/nlz088