Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Aug;142(8):1247-1262.
doi: 10.1007/s00439-023-02565-x. Epub 2023 Apr 28.

Cellular senescence and neurodegeneration

Kristopher Holloway  1 , Kashfia Neherin  1 , Kha Uyen Dam  1 , Hong Zhang  2
Affiliations
Review

Cellular senescence and neurodegeneration

Kristopher Holloway et al. Hum Genet. 2023 Aug.

Abstract

Advancing age is a major risk factor of Alzheimer's disease (AD). The worldwide prevalence of AD is approximately 50 million people, and this number is projected to increase substantially. The molecular mechanisms underlying the aging-associated susceptibility to cognitive impairment in AD are largely unknown. As a hallmark of aging, cellular senescence is a significant contributor to aging and age-related diseases including AD. Senescent neurons and glial cells have been detected to accumulate in the brains of AD patients and mouse models. Importantly, selective elimination of senescent cells ameliorates amyloid beta and tau pathologies and improves cognition in AD mouse models, indicating a critical role of cellular senescence in AD pathogenesis. Nonetheless, the mechanisms underlying when and how cellular senescence contributes to AD pathogenesis remain unclear. This review provides an overview of cellular senescence and discusses recent advances in the understanding of the impact of cellular senescence on AD pathogenesis, with brief discussions of the possible role of cellular senescence in other neurodegenerative diseases including Down syndrome, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis.

PubMed Disclaimer

References

    1. Abud EM, Ramirez RN, Martinez ES et al (2017) iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94:278-293.e9. https://doi.org/10.1016/j.neuron.2017.03.042 - DOI - PubMed - PMC
    1. Acklin S, Zhang M, Du W et al (2020) Depletion of senescent-like neuronal cells alleviates cisplatin-induced peripheral neuropathy in mice. Sci Rep 10:14170. https://doi.org/10.1038/s41598-020-71042-6 - DOI - PubMed - PMC
    1. Acosta JC, O’Loghlen A, Banito A et al (2008) Chemokine signaling via the CXCR2 receptor reinforces senescence. Cell 133:1006–1018. https://doi.org/10.1016/j.cell.2008.03.038 - DOI - PubMed
    1. Acosta JC, Banito A, Wuestefeld T et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15:978–990. https://doi.org/10.1038/ncb2784 - DOI - PubMed - PMC
    1. Adams PD (2007) Remodeling of chromatin structure in senescent cells and its potential impact on tumor suppression and aging. Gene 397:84–93. https://doi.org/10.1016/j.gene.2007.04.020 - DOI - PubMed - PMC

Substances

LinkOut - more resources