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Review
. 2020:155:203-234.
doi: 10.1016/bs.irn.2020.03.019. Epub 2020 Aug 11.

Cellular senescence in aging and age-related diseases: Implications for neurodegenerative diseases

Erin O Wissler Gerdes  1 , Yi Zhu  1 , B Melanie Weigand  1 , Utkarsh Tripathi  1 , Terence C Burns  1 , Tamar Tchkonia  1 , James L Kirkland  2
Affiliations
Review

Cellular senescence in aging and age-related diseases: Implications for neurodegenerative diseases

Erin O Wissler Gerdes et al. Int Rev Neurobiol. 2020.

Abstract

Aging is the major predictor for developing multiple neurodegenerative diseases, including Alzheimer's disease (AD) other dementias, and Parkinson's disease (PD). Senescent cells, which can drive aging phenotypes, accumulate at etiological sites of many age-related chronic diseases. These cells are resistant to apoptosis and can cause local and systemic dysfunction. Decreasing senescent cell abundance using senolytic drugs, agents that selectively target these cells, alleviates neurodegenerative diseases in preclinical models. In this review, we consider roles of senescent cells in neurodegenerative diseases and potential implications of senolytic agents as an innovative treatment.

Keywords: Alzheimer's disease; Cellular senescence; Dasatinib; Fisetin; Navitoclax; Parkinson's disease; Quercetin; Senescence-associated secretory phenotype; Senescent cell anti-apoptotic pathways; Senolytics.

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Conflict of interest statement

Competing financial interests J.L.K., T.T., and Y.Z. have a financial interest related to this research. Patents on senolytic drugs are held by Mayo Clinic. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. No conflicts of interest, financial or otherwise, are declared by E.O.W.G., B.M.W., U.T., or T.C.B.

Figures

Fig. 1
Fig. 1
Senescent human astrocytes. Primary human astrocytes were irradiated for 10Gy and studied 20days after irradiation. All of the astrocytes in this field exhibit increased SA-β-gal (blue).
Fig. 2
Fig. 2
Cellular senescence and neurodegenerative diseases.
See this image and copyright information in PMC

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