Authors
Mikolaj Ogrodnik, Yi Zhu, Larissa GP Langhi, Tamar Tchkonia, Patrick Krüger, Edward Fielder, Stella Victorelli, Rifqha A Ruswhandi, Nino Giorgadze, Tamar Pirtskhalava, Oleg Podgorni, Grigori Enikolopov, Kurt O Johnson, Ming Xu, Christine Inman, Marissa Schafer, Moritz Weigl, Yuji Ikeno, Terry C Burns, João F Passos, Thomas von Zglinicki, James L Kirkland, Diana Jurk
Publication date
2019/1/3
Journal
Cell Metabolism
Publisher
Cell Press
Description
Cellular senescence entails a stable cell-cycle arrest and a pro-inflammatory secretory phenotype, which contributes to aging and age-related diseases. Obesity is associated with increased senescent cell burden and neuropsychiatric disorders, including anxiety and depression. To investigate the role of senescence in obesity-related neuropsychiatric dysfunction, we used the INK-ATTAC mouse model, from which p16Ink4a-expressing senescent cells can be eliminated, and senolytic drugs dasatinib and quercetin. We found that obesity results in the accumulation of senescent glial cells in proximity to the lateral ventricle, a region in which adult neurogenesis occurs. Furthermore, senescent glial cells exhibit excessive fat deposits, a phenotype we termed "accumulation of lipids in senescence." Clearing senescent cells from high fat-fed or leptin receptor-deficient obese mice restored neurogenesis and alleviated …
Scholar articles
M Ogrodnik, YI Zhu, LGP Langhi, T Tchkonia, P Krüger… - Cell metabolism, 2019