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Reducing Senescent Cell Burden in Aging and Disease

Robert J Pignolo1, João F Passos1, Sundeep Khosla1

  • 1Mayo Clinic Departments of Medicine, Physiology and Biomedical Engineering, and the Kogod Center on Aging, Rochester, MN, USA.

Trends in Molecular Medicine
|June 27, 2020
PubMed

Insights

Cellular senescence, a key aging process, drives age-related diseases. Clearing senescent cells with senolytic drugs shows promise for improving healthspan and treating geriatric conditions.

Area of Science:

  • Gerontology and Cellular Biology
  • Molecular Biology and Aging Research

Background:

  • Cellular senescence is a fundamental aging process and a tumor suppressive mechanism.
  • Senescent cells accumulate with age, contributing to chronic diseases, geriatric syndromes, and multimorbidity.
  • This accumulation is linked to accelerated aging phenotypes in preclinical models.

Purpose of the Study:

  • To explore the potential of reducing senescent cell burden to prevent or alleviate aging-related diseases.
  • To investigate the hypothesis that pharmacologic interventions targeting senescent cells could transform geriatric medicine.

Main Methods:

  • Preclinical studies involving genetic and pharmacologic reduction of senescent cell burden in animal models.
  • Review of early-phase clinical trials assessing the safety and target engagement of senolytic agents.

Main Results:

  • Reduction of senescent cells in animals prevented, delayed, or alleviated various aging-related diseases.
  • Early clinical trials are evaluating senolytic agents for safety and efficacy.

Conclusions:

  • Targeting cellular senescence holds significant therapeutic potential for age-related conditions.
  • Senolytic therapies may offer transformative benefits for geriatric medicine and human healthspan.

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