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Senolytic agents lessen the severity of abdominal aortic aneurysm in aged mice
Exp Gerontol. 2021 May 19;111416. doi: 10.1016/j.exger.2021.111416.
Mojtaba Parvizi 1, Federico Franchi 2, Bonnie K Arendt 1, Sanam Ebtehaj 2, Martin Rodriguez-Porcel 2, Ian R Lanza 3
Abstract:
...Here we show that aging is associated with transcriptional changes in abdominal aortic tissue consistent with loss of smooth muscle cells, leukocyte adhesion, inflammation, and accumulation of senescent cells in the vascular wall and surrounding perivascular adipose tissue. Furthermore, aged mice demonstrated anatomical and histopathological features of AAA development in response to administration of angiotensin II over 28 days. Importantly, in our study we sought to determine if reducing senescent cells could lessen the severity of AAA in aged mice. We find that pretreatment of aged mice with oral senolytic agents (dasatinib + quercetin) reduced senescent cell abundance in the arterial walls and surrounding tissues and lessened the severity of AAA in response to angiotensin II administration. These data provide important preliminary evidence supporting a role of senescent cells in age-related AAA formation and progression and suggest that strategies to reduce senescent cell burden hold promise to lessen AAA severity.