Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span

Paul D. Robbins, Diana Jurk, Sundeep Khosla, James L. Kirkland, Nathan K LeBrasseur, Jordan D. Miller, João F. Passos, Robert J. Pignolo, Tamar Tchkonia, Laura J. Niedernhofer

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Senescence is the consequence of a signaling mechanism activated in stressed cells to prevent proliferation of cells with damage. Senescent cells (Sncs) often develop a senescence-associated secretory phenotype to prompt immune clearance, which drives chronic sterile inflammation and plays a causal role in aging and age-related diseases. Sncs accumulate with age and at anatomical sites of disease. Thus, they are regarded as a logical therapeutic target. Senotherapeutics are a new class of drugs that selectively kill Sncs (senolytics) or suppress their disease-causing phenotypes (senomorphics/senostatics). Since 2015, several senolytics went from identification to clinical trial. Preclinical data indicate that senolytics alleviate disease in numerous organs, improve physical function and resilience, and suppress all causes of mortality, even if administered to the aged. Here, we review the evidence that Sncs drive aging and disease, the approaches to identify and optimize senotherapeutics, and the current status of preclinical and clinical testing of senolytics.

Original languageEnglish (US)
Pages (from-to)779-803
Number of pages25
JournalAnnual Review of Pharmacology and Toxicology
Volume61
DOIs
StatePublished - Jan 6 2021

Keywords

  • aging
  • senescence
  • senescence-associated secretory phenotype
  • senolytics
  • senomorphics

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Senolytic Drugs: Reducing Senescent Cell Viability to Extend Health Span'. Together they form a unique fingerprint.

Cite this