Targeting senescent cells alleviates obesity‐induced metabolic dysfunction

Abstract Adipose tissue inflammation and dysfunction are associated with obesity‐related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug‐inducible “suicide” genes driven by the p16 Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating…

• AF
  American Federation for Aging Research
• GF
  Glenn Foundation for Medical Research
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BB/K019260/1, BB/M023389/1, BB/S006710/1, BB/K019260/1, BB/I020748/1, BB/M023389/1
• NI
  National Institute on Aging

  Awards: AG041122, AG31736, AG13925, AG46061, AG51661, AG044396
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases

  Award: DK50456