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Cellular Senescence: A Translational Perspective.

James L Kirkland1, Tamara Tchkonia1

  • 1Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, United States.

Ebiomedicine
|April 19, 2017
PubMed
Summary
This summary is machine-generated.

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Cellular senescence, a state of irreversible cell arrest, contributes to aging and disease. Researchers discovered senolytic agents that selectively eliminate senescent cells, potentially treating age-related conditions.

Area of Science:

  • Gerontology
  • Cell Biology
  • Molecular Biology

Background:

  • Cellular senescence is a state of irreversible cell cycle arrest characterized by resistance to apoptosis and a pro-inflammatory senescence-associated secretory phenotype (SASP).
  • Accumulation of senescent cells with aging and in disease contributes to inflammation, metabolic dysfunction, and tissue damage.
  • Reducing senescent cell burden shows promise in delaying or alleviating senescence-associated conditions.

Purpose of the Study:

  • To identify pro-survival pathways in senescent cells, termed Senescent Cell Anti-apoptotic Pathways (SCAPs).
  • To develop the first senolytic agents targeting these SCAPs, making senescent cells susceptible to apoptosis.
  • To evaluate the potential of senolytic agents in preclinical models for treating senescence-related conditions.
Keywords:
A1155463A1331852DasatinibFisetinNavitoclaxQuercetinSASP inhibitorsSenescent Cell Anti-apoptotic Pathways (SCAPs)Senolytics

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Main Methods:

  • Hypothesis-driven discovery of SCAPs.
  • Development of senolytic drugs based on identified SCAPs.
  • Preclinical testing of senolytic agents in relevant models.

Main Results:

  • Identification of specific SCAPs that maintain senescent cell survival.
  • Development of novel senolytic agents capable of inducing apoptosis in senescent cells.
  • Demonstration that senolytic agents alleviate multiple senescence-related phenotypes in preclinical studies.

Conclusions:

  • Senolytic agents targeting SCAPs represent a promising therapeutic strategy for combating aging and chronic diseases.
  • These agents have the potential to be transformative in clinical interventions for senescence-associated conditions.
  • Further translation into human clinical trials is underway.