The Role of Microglial Cellular Senescence in the Aging and Alzheimer Diseased Brain
Abstract
With each cell division, telomeres progressively shorten until they reach a critical length, at which point the cells enter cellular senescence. Microglia, a non-neuronal cell type residing within the central nervous system (CNS), play vital roles in maintaining neuronal function, health, and survival in both the normal and pathological CNS. A recent article described an increased incidence of microglial cytoplasmic structural abnormalities (i.e., swelling, twisted and shortened processes, and fragmentation) and dystrophy occurring in the cerebral cortex of human brains with age. These results suggest that microglial dystrophy may be a result of, or contribute to, their senescence, which in turn may impair their neuron-sustaining functions and ultimately lead to neuronal cell death.
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Microglia from aged human brains are generally swollen and show fragmentation of processes thought to contribute to neuronal death.
“Indeed, microglia from aged human brains are generally swollen and show fragmentation of processes thought to contribute to neuronal death [38].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [38]
Cites
Streit, W. J., Walter, S. A., & Pennell, N. A. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00069-0 · Cited by 1,096 · see citing works
Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice
Eglitis, M. A., & Mezey, É. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4080 · Cited by 1,015 · see citing works
Microglia as neuroprotective, immunocompetent cells of the CNS
Streit, W. J. (2002) · Glia · doi:10.1002/glia.10154 · Cited by 919 · see citing works
Dystrophic microglia in the aging human brain
Streit, W. J., Sammons, N. W., Kuhns, A. J., & Sparks, D. L. (2004) · Glia · doi:10.1002/glia.10319 · Cited by 705 · see citing works
Identification of normal and pathological aging in prospectively studied nondemented elderly humans
Dickson, D. W., Crystal, H. A., Mattiace, L. A., Masur, D. M., Blau, A. D., Davies, P., Yen, S.-H., & Aronson, M. K. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90027-u · Cited by 643 · see citing works
Age-specific incidence rates of Alzheimer’s disease: The Baltimore Longitudinal Study of Aging
Kawas, C., Gray, S., Brookmeyer, R., Fozard, J., & Zonderman, A. (2000) · Neurology · doi:10.1212/wnl.54.11.2072 · Cited by 472 · see citing works
Brain macrophages: evaluation of microglia and their functions
Thomas, W. E. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90007-9 · Cited by 441 · see citing works
Microglial cells but not astrocytes undergo mitosis following rat facial nerve axotomy
Graeber, M. B., Tetzlaff, W., Streit, W. J., & Kreutzberg, G. W. (1988) · Neuroscience Letters · doi:10.1016/0304-3940(88)90585-x · Cited by 333 · see citing works
Streit, W. J., & Colton, C. A. (1995) · Scientific American · doi:10.1038/scientificamerican1195-54 · Cited by 171 · see citing works
Progressive telomere shortening occurs in cultured rat microglia, but not astrocytes
Flanary, B. E., & Streit, W. J. (2004) · Glia · doi:10.1002/glia.10301 · Cited by 167 · see citing works
Self-citationFrautschy, S. A., Cole, G. M., & Baird, A. (1992) · PubMed Central · Cited by 157 · see citing works
How HIV Defeats the Immune System
Nowak, M. A., & McMichael, A. J. (1995) · Scientific American · doi:10.1038/scientificamerican0895-58 · Cited by 125 · see citing works
Telomeres Shorten with Age in Rat Cerebellum and Cortex <i>in vivo</i>
Flanary, B. E., & Streit, W. J. (2003) · Journal of Anti-Aging Medicine · doi:10.1089/109454503323028894 · Cited by 85 · see citing works
Self-citationMann, D. M. A., & Yates, P. O. (1981) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(81)90056-7 · Cited by 19 · see citing works
Physiology and Pathophysiology of Microglial Cell Function
Streit, W. J. (2002) · Springer eBooks · doi:10.1007/978-1-4757-4139-1_1 · Cited by 14 · see citing works
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Cellular senescence and the aging brain
Chinta, S. J., Woods, G., Rane, A., Demaria, M., Campisi, J., & Andersen, J. K. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2014.09.018 · Cited by 282 · see citing works
Evidence That Aging And Amyloid Promote Microglial Cell Senescence
Flanary, B. E., Sammons, N. W., Nguyen, C., Walker, D., & Streit, W. J. (2007) · Rejuvenation Research · doi:10.1089/rej.2006.9096 · Cited by 272 · see citing works
Self-citationMicroglia in the aging brain: relevance to neurodegeneration
Luo, X.-G., Ding, J.-Q., & Chen, S.-D. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-12 · Cited by 236 · see citing works
“However, both compromised amyloid-clearing ability of microglia[80] and the damage of microglia by amyloid[81] have been reported in AD brain.”
BackgroundParkinson’s disease as a result of aging
Rodriguez, M., Rodriguez‐Sabate, C., Morales, I., Sanchez, A., & Sabate, M. (2015) · Aging Cell · doi:10.1111/acel.12312 · Cited by 214 · see citing works
Astrocyte Senescence and Alzheimer’s Disease: A Review
Han, X., Zhang, T., Liu, H., Mi, Y., & Gou, X. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00148 · Cited by 177 · see citing works
Chinta, S. J., Lieu, C. A., DeMaria, M., Laberge, R. ‐., Campisi, J., & Andersen, J. K. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12029 · Cited by 165 · see citing works
“A comparative study examining both young and old autopsied human brains demonstrated that, with age, microglia transform morphologically from ramified to hypertrophic and dystrophic forms characterized by loss of fine branches (deramification), formation of cytoplasmic spheroids, beading and fragmentation [75, 76].”
Microglia change from a reactive to an age-like phenotype with the time in culture
Caldeira, C., Oliveira, A. F., Cunha, C., Vaz, A. R., Falcão, A. S., Fernandes, A., & Brites, D. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00152 · Cited by 156 · see citing works
Callaghan, T. M., & Wilhelm, K. ‐. (2008) · International Journal of Cosmetic Science · doi:10.1111/j.1468-2494.2008.00454.x · Cited by 149 · see citing works
DNA repair deficiency and senescence in concussed professional athletes involved in contact sports
Schwab, N., Grenier, K., & Hazrati, L.-N. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0822-3 · Cited by 47 · see citing works
- Authors
- Flanary, B.
- Affiliations
- University of Florida Health (US)
- Corresponding author
- Flanary, Barry
- Venue
- Rejuvenation Research
- Publisher
- SAGE Publications
- Published
- 2005-06
- Volume
- 8
- Issue
- 2
- Pages
- 82-85
- ISSN
- 1094-5458 (ISSN-L)
- 1549-1684
- 1557-8577
- OpenAlex
- W2043122628
- Cited by
- 40
- References
- 15
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 3 · 2014: 4 · 2013: 1
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Rejuvenation Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- telomere shortening, brain aging, Alzheimer's disease, neuronal cell death, neuroinflammation, cerebral cortex
- MeSH terms
- Aging, Alzheimer Disease, Brain, Humans, Cellular Senescence, Microglia
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