IPA Improves Muscle Function and Reduces Bone Loss in Aged Mice and Modulate Lifespan in Drosophila melanogaster

TL;DR

A tryptophan metabolite called IPA improves muscle function and bone health in aged mice and extends lifespan in fruit flies, suggesting potential for treating age-related decline.

Contribution

IPA is identified as a novel microbiota-derived compound that enhances musculoskeletal health and modulates lifespan in model organisms.

Findings

IPA treatment improved muscle function in aged mice without changing muscle fiber size.

IPA enhanced bone microarchitecture and reduced oxidative stress and senescence.

IPA extended the lifespan of Drosophila melanogaster in a genotype- and sex-specific manner.

Abstract

Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contribute to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived tryptophan (TRP) metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice. Additionally, we assessed the impact of IPA on the lifespan of the fruit fly, Drosophila melanogaster. Our findings revealed that IPA-treated aged mice exhibited enhanced muscle function (grip strength and hang time). Histological and bone microCT analyses revealed no changes in muscle fiber size but enhanced bone microarchitecture. Furthermore, molecular studies have elucidated that IPA treatment prevents oxidative stress and reduces senescence, indicating improved cellular survival. Our Drosophila melanogaster longevity analysis revealed a significant extension of lifespan, but lifespan effects were genotype- and sex-specific. Collectively, our findings identify IPA as a promising microbiota-derived metabolite that improves musculoskeletal health and promotes longevity, highlighting its potential as a therapeutic intervention for age-related decline.