Tier 4 — mechanistic

Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents

Ryu D, Mouchiroud L, Andreux PA, Katsyuba E, Moullan N, Nicolet-Dit-Félix AA, Williams EG, Jha P, Lo Sasso G, Huzard D, Aebischer P, Sandi C, Rinsch C, Auwerx J

Nature Medicine 2016 22(8):879-888

Bibliography

PubMed: PMID 27400265
DOI: 10.1038/nm.4132
Funding: Supported by EPFL and Swiss National Science Foundation grants. Amazentis SA, co-founded by several authors, is the company later formed to commercialise urolithin A based on these findings.
Competing interests: Authors Andreux and Rinsch are affiliated with Amazentis SA, the company formed to commercialise urolithin A based on these findings.

Study snapshot

Design	Preclinical mechanistic study: in vitro mitophagy assays, C. elegans lifespan/healthspan assays, and rodent (mouse and rat) exercise-capacity studies
Model	C. elegans, aged mice, young rats, cultured myoblasts
Sample	Not applicable — preclinical animal/cell study
Intervention	Oral/dietary urolithin A administration in C. elegans and rodent models
Duration	Chronic feeding studies (lifespan-duration in C. elegans; multi-week feeding in rodents)
Endpoints	Mitophagy induction (in vitro and in vivo); C. elegans lifespan and healthspan (mobility, pharyngeal pumping); Rodent exercise capacity/muscle function

What the study showed, in plain terms

This is the founding study establishing urolithin A as a compound that triggers mitophagy, the clearance of damaged mitochondria. In worms it extended lifespan and preserved mobility with age. In aged mice and young rats it improved muscle exercise capacity. This is animal and cell research, not a human trial, but it is the mechanistic basis for the later human urolithin A trials.

Key findings

Urolithin A induced mitophagy in vitro and in vivo, extended lifespan and preserved mobility and pharyngeal pumping in C. elegans with age, and improved exercise capacity in two mouse models of age-related muscle decline as well as in young rats.

What this study can and cannot tell us

All findings are preclinical (nematode and rodent models); no human data. Animal dosing does not directly translate to a human supplemental dose. Two authors are affiliated with the company later formed to commercialise urolithin A.

Citation network

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Biohack Blueprint analyses that reference this study in their evidence base.

Jul 11, 2026 Fisetin vs Urolithin A: Senolytic vs Mitophagy (2026)Fisetin is studied for senotherapeutic effects; urolithin A targets mitophagy. Urolithin A has the more developed human intervention literature, while human systemic...Read analysis

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction

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