Deleted in Breast Cancer 1 regulates cellular senescence during obesity

Aging Cell

Carlos Escande²  Veronica Nin²  Tamar Pirtskhalava³  Claudia C. Chini²  Maria Thereza Barbosa²  Angela Mathison¹  Raul Urrutia¹  Tamar Tchkonia³  James L. Kirkland³ 

[1] Laboratory of Epigenetics and Chromatin Dynamics, Mayo Clinic, Rochester, MN, USA;Department of Anesthesia, Mayo Clinic, Rochester, MN, USA;Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA

关键词: aging;    hdacs;    mice;    obesity;    senescence;    signaling;    Sir2;   

DOI  :  10.1111/acel.12235

来源: Wiley

【 摘 要 】

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 (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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.