Anti-aging: senolytics or gerostatics (unconventional view)

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.