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Senolytic treatment attenuates immune cell infiltration without improving IAV outcomes in aged mice

  • 0Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Aging Cell +

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January 4, 2025

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January 4, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Senolytic treatments, used to clear aging cells, did not improve outcomes in aged mice infected with influenza A virus. These drugs failed to reduce lung damage or enhance survival, suggesting they may not universally combat age-related immune issues in respiratory infections.

Area Of Science

  • Gerontology
  • Immunology
  • Virology

Background

  • Aging is a significant risk factor for severe outcomes in respiratory infections.
  • Senescent cells accumulate with age, promoting inflammation and worsening infection severity.
  • Senolytics have shown promise in coronavirus models but their role in influenza A viral infections is unclear.

Purpose Of The Study

  • To investigate the efficacy of senolytic treatments in improving outcomes for aged mice infected with influenza A virus (IAV).
  • To determine if senolytics can reduce mortality and weight loss associated with IAV infection in older mice.

Main Methods

  • Aged mice were infected with influenza A virus (IAV).
  • Three senolytic regimens were administered: dasatinib plus quercetin, fisetin, and ABT-263.
  • Outcomes measured included survival, weight loss, and immune cell infiltration in the lungs.

Main Results

  • None of the tested senolytic regimens (dasatinib plus quercetin, fisetin, ABT-263) improved survival or reduced weight loss in aged mice infected with IAV.
  • Dasatinib plus quercetin and fisetin treatments exacerbated immune suppression compared to aging alone.
  • Short-term senolytic treatment did not significantly reduce markers of senescence in the aged mouse model.

Conclusions

  • Acute senolytic treatment does not universally improve outcomes for aged mice experiencing respiratory viral infections like influenza A.
  • The tested senolytic agents failed to reverse the aging-related immune phenotype in this model.
  • Further research is needed to understand the complex interplay between senescence, aging, and viral immunity.

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