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Q. Behfar, A. Ramirez Zuniga, P.V. Martino-Adami

J Prev Alz Dis 2022;3(9):523-531

The underlying processes occurring in aging are complex, involving numerous biological changes that result in chronic cellular stress and sterile inflammation. One of the main hallmarks of aging is senescence. While originally the term senescence was defined in the field of oncology, further research has established that also microglia, astrocytes and neurons become senescent. Since age is the main risk factor for neurodegenerative diseases, it is reasonable to argue that cellular senescence might play a major role in Alzheimer’s disease. Specific cellular changes seen during Alzheimer’s disease are similar to those observed during senescence across all resident brain cell types. Furthermore, increased levels of senescence-associated secretory phenotype proteins such as IL-6, IGFBP, TGF-β and MMP-10 have been found in both CSF and plasma samples from Alzheimer’s disease patients. In addition, genome-wide association studies have identified that individuals with Alzheimer’s disease carry a high burden of genetic risk variants in genes known to be involved in senescence, including ADAM10, ADAMTS4, and BIN1. Thus, cellular senescence is emerging as a potential underlying disease process operating in Alzheimer’s disease. This has also attracted more attention to exploiting cellular senescence as a therapeutic target. Several senolytic compounds with the capability to eliminate senescent cells have been examined in vivo and in vitro with notable results, suggesting they may provide a novel therapeutic avenue. Here, we reviewed the current knowledge of cellular senescence and discussed the evidence of senescence in various brain cell types and its putative role in inflammaging and neurodegenerative processes.

Q. Behfar ; A. Ramirez Zuniga ; P.V. Martino-Adami ; (2022): Aging, Senescence, and Dementia. The Journal of Prevention of Alzheimer’s Disease (JPAD).

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