Deleted in Breast Cancer 1 regulates cellular senescence during obesity. Aging Cell 2014 Oct;13(5):951-3
Date
07/06/2014Pubmed ID
24992635Pubmed Central ID
PMC4172532DOI
10.1111/acel.12235Scopus ID
2-s2.0-84940363648 17 CitationsAbstract
Chronic obesity leads to inflammation, tissue dysfunction, and cellular senescence. It was proposed that cellular senescence during obesity and aging drives inflammation and dysfunction. Consistent with this, clearance of senescent cells increases healthspan in progeroid mice. Here, we show that the protein Deleted in Breast Cancer-1 (DBC1) regulates cellular senescence during obesity. Deletion of DBC1 protects preadipocytes against cellular senescence and senescence-driven inflammation. Furthermore, we show protection against cellular senescence in DBC1 KO mice during obesity. Finally, we found that DBC1 participates in the onset of cellular senescence in response to cell damage by mechanism that involves binding and inhibition of HDAC3. We propose that by regulating HDAC3 activity during cellular damage, DBC1 participates in the fate decision that leads to the establishment of cellular senescence and consequently to inflammation and tissue dysfunction during obesity.
Author List
Escande C, Nin V, Pirtskhalava T, Chini CC, Thereza Barbosa M, Mathison A, Urrutia R, Tchkonia T, Kirkland JL, Chini ENAuthors
Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of WisconsinRaul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAging
Animals
Cellular Senescence
DNA Damage
Female
Inflammation
Mice
Mice, Knockout
Obesity
