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Bussian TJ, Aziz A, Meyer CF, Swenson BL, van Deursen JM, Baker DJ. Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature. 2018 Oct;562(7728):578-582. Epub 2018 Sep 19 PubMed.
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University of Pennsylvania
Both these papers are important because they open up new lines for investigating the impact of aging-related neurodegenerative diseases, and we know so little about how mechanisms of aging interact with or contribute to mechanisms of neurodegeneration. Thus, as Bussian et al. note, markers of senescence are present in human neurodegenerative diseases, but the significance of this was not clear. Now, Bussian et al. show that tau Tg mice accumulate p16INK4A-positive senescent astrocytes and microglia and that elimination of these cells genetically and with first-generation senolytic stops gliosis, hyperphosphorylation of both soluble and insoluble tau, neurofibrillary tangles, and neurodegeneration. These findings suggest senescent cells contribute to the initiation and progression of tau-mediated disease. Hence, senescent cells could be a logical target for therapies to treat neurodegenerative disease, but obviously further replication will be needed for these novel results, and this is provided in large part by the second paper by Musi et al. who show that treatment of tau-transgenic mice with senolytics to remove senescent cells also showed a beneficial therapeutic response including reducing tangles, neuron loss, and ventricular enlargement. Together these studies support the notion that senescent cells may play a role in aging-related tauopathies.View all comments by John Trojanowski
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