Cellular senescence and the aging brain
Open accessAbstract
Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex 'senescence-associated secretory phenotype' (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative and hyperplastic. While cellular senescence in peripheral tissues has recently been linked to a number of age-related pathologies, its involvement in brain aging is just beginning to be explored. Recent data generated by several laboratories suggest that both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain. Moreover, this increase correlates with neurodegeneration. Senescent cells in the brain could therefore constitute novel therapeutic targets for treating age-related neuropathologies.
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In many prevalent neurodegenerative conditions including Alzheimer's Disease, brain tissue biopsies have increased levels of p16INK4a-positive astrocytes, MMP-1 and IL-6.
“In many prevalent neurodegenerative conditions including Alzheimer's Disease, brain tissue biopsies are present with increased levels of p16INK4a- positive astrocytes, MMP-1 and IL-6”
From Redox control of senescence and age-related disease. (2017) · cites this paper as [100]
Senescent cells accumulate with age, neurodegenerative disease and cognitive decline, neuropsychiatric disorders, and after TBI.
“Senescent cells accumulate with age [23, 157, 175], neurodegenerative disease and cognitive decline [15], neuropsychiatric disorders [33], and have recently been discovered to accumulate after TBI [3, 123, 131, 132, 151].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [23]
Diseases associated with the accumulation of senescent cells, such as neurodegenerative disorders, osteoarthritis and idiopathic pulmonary fibrosis, exhibit iron dyshomeostasis, where iron burden often correlates with disease severity.
“Diseases associated with the accumulation of senescent cells, such as neurodegenerative disorders (e.g. Alzheimer's and Parkinson's) [20], [21], [22], osteoarthritis [23], [24] and idiopathic pulmonary fibrosis [25], also exhibit iron dyshomeostasis where often iron burden correlates with disease severity [14], [15], [26], [27], [28], [29], [30], [31], [32], [33], [34].”
From Iron accumulation in senescent cells is coupled with impaired ferritinophagy and inhibition of ferroptosis (2018) · cites this paper as [20]
Cellular senescence is detrimental to overall brain health through its various effects on different cell types.
“Cellular senescence is detrimental to overall brain health, through its various effects on different cell types [19].”
From DNA repair deficiency and senescence in concussed professional athletes involved in contact sports (2019) · cites this paper as [19]
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- Authors
- Chinta, S. J., Woods, G., Rane, A., Demaria, M., Campisi, J., & Andersen, J. K.
- Affiliations
- Buck Institute for Research on Aging (US)
- Corresponding author
- Andersen, Julie K.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2015-08
- Volume
- 68
- Pages
- 3-7
- ISSN
- 0531-5565 (ISSN-L)
- PMC
- PMC4382436
- OpenAlex
- W2057204948
- Cited by
- 282
- References
- 79
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 27 · 2023: 18 · 2022: 22 · 2021: 40 · 2020: 28 · 2019: 34 · 2018: 28 · 2017: 18 · 2016: 15 · 2015: 6 · 2014: 1
- FWCI
- 8.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ellison Senior Scholar Fellowship
- 2014 Buck Impact Circle
- NIA PPG (AG025901)
- CIRM (TG2-01155)
- American Italian Cancer Foundation
- T32 (AG000266)
- NIA R37 (AG009909)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Keywords
- cellular senescence, brain aging, senescence-associated secretory phenotype, neurodegeneration, senescent cells, non-neuronal cells, inflammatory cytokines, senolytics
- MeSH terms
- Aging, Animals, Brain, Humans, Models, Neurological, Cellular Senescence, Neurodegenerative Diseases, Cell Proliferation, Mice
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