Tier 2 — strong

Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial

Denk D, Singh A, Kasler HG, D'Amico D, Rey J, Alcober-Boquet L, Gorol JM, Steup C, Tiwari R, Kwok R, Argüello RJ, Faitg J, Sprinzl K, Zeuzem S, Nekljudova V, Loibl S, Verdin E, Rinsch C, Greten FR
Nature Aging 2025 5(11):2309-2322

Bibliography

PubMed
PMID 41174221
PubMed Central
PMC12618261
DOI
10.1038/s43587-025-00996-x
Trial registry
View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.
Funding
Amazentis SA funded the clinical study and provided the investigational product (Mitopure).
Competing interests
Amazentis employees and its president/board delegate were authors; the senior academic investigator reported consulting fees from Amazentis, and one author reported travel compensation from Amazentis.

Study snapshot

DesignRandomized, double-blind, placebo-controlled MitoImmune trial
ModelHealthy middle-aged adults aged 45-70 years
Sample50 randomized, 25 per group
InterventionUrolithin A 1,000 mg/day versus placebo
Duration28 days
EndpointsPeripheral T-cell phenotypes; CD8+ fatty-acid oxidation capacity; Immune-cell mitochondrial biogenesis; NK-cell and monocyte populations; Cytokines and immune function

What the study showed, in plain terms

The 2025 MitoImmune trial gave 50 healthy middle-aged adults 1,000 mg/day Urolithin A or placebo for four weeks. Urolithin A shifted several immune-cell populations toward less terminally differentiated phenotypes and increased CD8+ fatty-acid oxidation and mitochondrial biogenesis. These are human immune-aging target-engagement findings, not evidence that the supplement prevents infections or extends life.

Key findings

Naive-like, less terminally exhausted CD8+ cells increased versus placebo.

CD8+ fatty-acid oxidation capacity increased significantly.

Mitochondrial biogenesis and several innate immune-cell populations changed in the treated group.

The trial supports direct human immune/metabolic target engagement.

What this study can and cannot tell us

Four weeks is too short for clinical aging or infection outcomes.

The outcomes are cellular and functional biomarkers rather than disease endpoints.

Amazentis funded the study and had multiple employee authors.

Editorial review

Reviewed by the Biohack Blueprint research team

Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology