2. Academic Validation
  3. Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes

Targeted Elimination of Senescent Beta Cells Prevents Type 1 Diabetes

  • Cell Metab. 2019 May 7;29(5):1045-1060.e10. doi: 10.1016/j.cmet.2019.01.021.
Peter J Thompson 1,  Ajit Shah 1,  Vasilis Ntranos 2,  Frederic Van Gool 1,  Mark Atkinson 3,  Anil Bhushan 4
Affiliations

Affiliations

  • 1 Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 2 Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
  • 3 Diabetes Institute, University of Florida, Gainesville, FL 32610-0296, USA.
  • 4 Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: [email protected].
PMID: 30799288 DOI: 10.1016/j.cmet.2019.01.021
Abstract

Type 1 diabetes (T1D) is an organ-specific autoimmune disease characterized by hyperglycemia due to progressive loss of pancreatic beta cells. Immune-mediated beta cell destruction drives the disease, but whether beta cells actively participate in the pathogenesis remains unclear. Here, we show that during the natural history of T1D in humans and the non-obese diabetic (NOD) mouse model, a subset of beta cells acquires a senescence-associated secretory phenotype (SASP). Senescent beta cells upregulated pro-survival mediator Bcl-2, and treatment of NOD mice with Bcl-2 inhibitors selectively eliminated these cells without altering the abundance of the immune cell types involved in the disease. Significantly, elimination of senescent beta cells halted immune-mediated beta cell destruction and was sufficient to prevent diabetes. Our findings demonstrate that beta cell senescence is a significant component of the pathogenesis of T1D and indicate that clearance of senescent beta cells could be a new therapeutic approach for T1D.

Keywords

DNA damage; SASP; beta cells; cellular senescence; senolytics; type 1 diabetes.

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