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Deleted in Breast Cancer 1 regulates cellular senescence during obesity. Aging Cell 2014 Oct;13(5):951-3

Date

07/06/2014

Pubmed ID

24992635

Pubmed Central ID

PMC4172532

DOI

10.1111/acel.12235

Scopus ID

2-s2.0-84940363648   17 Citations

Abstract

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 EN

Authors

Angela Mathison PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Raul 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 Transducing
Aging
Animals
Cellular Senescence
DNA Damage
Female
Inflammation
Mice
Mice, Knockout
Obesity