Microbiota-derived indole-3-propionic acid extends lifespan in Drosophila and improves muscle and bone health in mice

Sagar Vyavahare1, Ford Berger1, Shelton G Swint2

  • 1Department of Medicine, Augusta University, Augusta, GA, 30912, USA.

Geroscience
|January 16, 2026
PubMed

Insights

Indole-3-propionic acid (IPA), a gut microbe metabolite, improved muscle and bone health in aged mice. IPA also extended lifespan in fruit flies, showing potential for treating age-related functional decline.

Area of Science:

  • Microbiology
  • Gerontology
  • Metabolomics

Background:

  • Aging alters tryptophan (TRP) metabolism, impacting musculoskeletal health.
  • Microbiota-derived metabolites play a role in age-related changes.
  • Indole-3-propionic acid (IPA) is a TRP metabolite with potential health implications.

Purpose of the Study:

  • To investigate the effects of IPA on musculoskeletal health in aged mice.
  • To examine IPA's impact on lifespan in Drosophila melanogaster.
  • To elucidate the molecular mechanisms underlying IPA's effects.

Main Methods:

  • Aged mice received subcutaneous IPA injections for 12 weeks.
  • Drosophila melanogaster were fed IPA supplemented food throughout their lifespan.
  • Assessed muscle function, bone microarchitecture, oxidative stress, senescence, and lifespan.

Main Results:

  • IPA treatment enhanced grip strength and hang time in aged mice.
  • Bone microarchitecture improved in IPA-treated mice, with no changes in muscle fiber size.
  • IPA prevented oxidative stress and reduced senescence, improving cellular survival.
  • IPA significantly extended lifespan in Drosophila melanogaster, with genotype- and sex-specific effects.

Conclusions:

  • IPA, a microbiota-derived metabolite, improves musculoskeletal health in aged mice.
  • IPA shows potential for promoting longevity and combating age-related functional decline.
  • IPA represents a promising therapeutic target for interventions against aging.