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SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
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Anti-aging: senolytics or gerostatics (unconventional view).

Mikhail V Blagosklonny1

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Summary

Senolytics, drugs targeting senescent cells, may extend lifespan by inhibiting aging pathways, similar to gerostatics like rapamycin. Further research is needed to confirm their efficacy and mechanisms for organismal aging.

Keywords:
aginggerosciencehyperfunction theorysenolyticssirolimus

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Area of Science:

  • Gerontology
  • Pharmacology
  • Oncology

Background:

  • Senolytics are anti-cancer drugs repurposed to selectively eliminate senescent cells.
  • Selective elimination of senescent cells presents significant challenges, comparable to targeting cancer cells.

Purpose of the Study:

  • To propose strategies for developing selective senolytics by leveraging oncogene-addiction and drug combinations.
  • To discuss gerostatics, such as rapamycin and mTOR inhibitors, which slow cellular aging.
  • To explore the potential of senolytics and gerostatics in extending lifespan.

Main Methods:

  • Exploiting oncogene-addiction principles from cancer therapy for senolytic selectivity.
  • Investigating gerostatic drugs that inhibit growth- and aging-promoting pathways (e.g., mTOR inhibitors).
  • Reviewing existing studies on senolytics (fisetin, Dasatinib plus Quercetin) and their effects on lifespan in mice.

Main Results:

  • Senolytics may extend lifespan, potentially through mTOR pathway inhibition, exhibiting gerostatic-like effects.
  • Gerostatics, including rapamycin and mTOR inhibitors, consistently demonstrate lifespan extension across various inhibition methods.
  • Current evidence suggests senolytics' life-extending effects in mice are modest and possibly linked to gerostatic activity.

Conclusions:

  • Developing selective senolytics is challenging, but strategies combining drug therapies show promise.
  • Gerostatics offer a distinct approach by slowing cellular aging without cell death, with established lifespan-extending benefits.
  • The lifespan extension observed with certain senolytics might be attributable to their indirect gerostatic (mTOR-inhibiting) properties rather than direct senolysis.