{"id":"doi:10.1016/j.cmet.2018.12.008","kind":"article","title":"Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis","authors":["Ogrodnik M","Zhu Y","Langhi LGP","Tchkonia T","Krüger P","Fielder E","Victorelli S","Ruswhandi RA","Giorgadze N","Pirtskhalava T","Podgorni O","Enikolopov G","Johnson KO","Xu M","Inman C","Palmer AK","Schafer M","Weigl M","Ikeno Y","Burns TC","Passos JF","von Zglinicki T","Kirkland JL","Jurk D"],"author_count":24,"year":2019,"published":"2019-01-03","venue":"Cell metabolism","cited_by":404,"doi":"10.1016/j.cmet.2018.12.008","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cmet.2018.12.008","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cmet.2018.12.008","updated":null,"pmid":"30612898","pmcid":"PMC6509403","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6509403/pdf","abstract":"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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis\" by Ogrodnik M, Zhu Y, Langhi LGP et al., https://doi.org/10.1016/j.cmet.2018.12.008, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}