Open AccessDeleted in B reast C ancer 1 regulates cellular senescence during obesity
Author(s) -
Escande Carlos,
Nin Veronica,
Pirtskhalava Tamar,
Chini Claudia C.,
Thereza Barbosa Maria,
Mathison Angela,
Urrutia Raul,
Tchkonia Tamar,
Kirkland James L.,
Chini Eduardo N.
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12235
Subject(s) - senescence , inflammation , biology , microbiology and biotechnology , hdac3 , immunology , genetics , gene , histone deacetylase , histone
Summary 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 ( DBC 1) regulates cellular senescence during obesity. Deletion of DBC 1 protects preadipocytes against cellular senescence and senescence‐driven inflammation. Furthermore, we show protection against cellular senescence in DBC 1 KO mice during obesity. Finally, we found that DBC 1 participates in the onset of cellular senescence in response to cell damage by mechanism that involves binding and inhibition of HDAC 3. We propose that by regulating HDAC 3 activity during cellular damage, DBC 1 participates in the fate decision that leads to the establishment of cellular senescence and consequently to inflammation and tissue dysfunction during obesity.