| First Author | Ogrodnik M | Year | 2019 |
| Journal | Cell Metab | Volume | 29 |
| Issue | 5 | Pages | 1061-1077.e8 |
| PubMed ID | 30612898 | Mgi Jnum | J:274955 |
| Mgi Id | MGI:6303469 | Doi | 10.1016/j.cmet.2018.12.008 |
| Citation | Ogrodnik M, et al. (2019) Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis. Cell Metab 29(5):1061-1077.e8 |
| abstractText | 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 p16(Ink4a)-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 anxiety-related behavior. Our study provides proof-of-concept evidence that senescent cells are major contributors to obesity-induced anxiety and that senolytics are a potential new therapeutic avenue for treating neuropsychiatric disorders. |
