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Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

35.0K

Targeting senescent cells alleviates obesity-induced metabolic dysfunction

Allyson K Palmer1,2,3, Ming Xu1,4, Yi Zhu1

  • 1Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, Minnesota.

Aging Cell
|March 26, 2019
PubMed

Insights

Cellular senescence drives obesity-related metabolic dysfunction. Eliminating senescent cells with senolytic agents improved insulin sensitivity, reduced inflammation, and ameliorated diabetes complications in mice.

Area of Science:

  • Metabolic research
  • Cellular biology
  • Immunology

Background:

  • Adipose tissue inflammation and dysfunction link obesity to insulin resistance and diabetes.
  • Cellular senescence, characterized by accumulating senescent cells, is observed in obesity but its direct role in diabetes pathogenesis is unproven.

Purpose of the Study:

  • To investigate the pathogenic role of cellular senescence in obesity-related metabolic dysfunction.
  • To evaluate the therapeutic potential of senolytic interventions in ameliorating metabolic and adipose tissue dysfunction.

Main Methods:

  • Utilized drug-inducible "suicide" genes (p16Ink4a promoter) and senolytic agents to reduce senescent cell burden in obese mice.
  • Assessed metabolic parameters including glucose tolerance, insulin sensitivity, and inflammatory markers.
  • Examined adipose tissue characteristics, immune cell infiltration (monocytes, macrophages), and organ function (kidney, heart).

Main Results:

  • Senolytic interventions significantly improved glucose tolerance and insulin sensitivity in obese mice.
  • Reduced circulating inflammatory mediators and promoted adipogenesis in adipose tissue.
  • Prevented monocyte migration and decreased macrophage accumulation in adipose tissue, alongside improvements in microalbuminuria, podocyte function, and cardiac diastolic function.

Conclusions:

  • Cellular senescence is a causal factor in obesity-induced inflammation and metabolic derangements.
  • Senolytic agents demonstrate therapeutic promise for treating obesity-related metabolic dysfunction and associated complications.
Keywords:
adipogenesisagingcellular senescencedasatinibquercetinsenolyticstype 2 diabetes

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