Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2019 Jan 8

PMID 30612898

Citations 205

Authors

Mikolaj Ogrodnik

Yi Zhu

Larissa G P Langhi

Tamar Tchkonia

Patrick Kruger

Edward Fielder

Stella Victorelli

Rifqha A Ruswhandi

Nino Giorgadze

Tamar Pirtskhalava

Oleg Podgorni

Grigori Enikolopov

Kurt O Johnson

Ming Xu

Christine Inman

Allyson K Palmer

Marissa Schafer

Moritz Weigl

Yuji Ikeno

Terry C Burns

Joao F Passos

Thomas von Zglinicki

James L Kirkland

Diana Jurk

Affiliations

Soon will be listed here.

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-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.

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