Ultimate Longevity Bible

Concept

Senotherapeutic

Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

Two branches

Senolytic

Drugs that selectively kill senescent cells while sparing healthy ones, exploiting the senescence-cell anti-apoptotic pathways (SCAPs). Examples:

  • Dasatinib + quercetin combination.
  • Fisetin.
  • Navitoclax (ABT-263): potent but haematologically toxic.
  • UBX0101, UBX1325: locally-delivered for joint and eye indications.
  • Cardiac glycosides (digoxin, ouabain): newer senolytic class.

Senomorphic

Drugs that silence the SASP (senescence-associated secretory phenotype) without killing the cells. Examples:

  • Rapamycin (the canonical senomorphic).
  • JAK inhibitors (ruxolitinib).
  • NF-κB inhibitors.
  • Metformin has senomorphic effects.

Why the distinction matters

  • Senolytics clear the cell burden — potentially lasting effect per intermittent dose; risk of clearing useful senescent populations (wound healing, embryogenesis).
  • Senomorphics suppress secretion — continuous use required; spare cell populations but don’t reduce burden.

Current state

  • Most senolytic trials use the dasatinib + quercetin combination or fisetin.
  • No senotherapeutic is FDA-approved for longevity indications.
  • First-in-human pilot data exist for diabetic kidney disease, IPF, AMD, frailty.

Related entries

Senolytics, Fisetin, Cellular senescence, Geroprotector, Unity Biotechnology.

References

  • Kirkland, J. L. & Tchkonia, T. Senolytic drugs: from discovery to translation. J. Intern. Med. 288, 518–536 (2020).

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