Four weeks of urolithin A shifted immune cell composition and function in healthy middle-aged adults in ways consistent with less immune aging.
Evidence
This randomized, double-blind, placebo-controlled trial in 50 healthy middle-aged adults found that oral urolithin A for 4 weeks increased naive-like less terminally exhausted CD8 cells and CD8 fatty acid oxidation capacity, alongside secondary changes in NK cells, monocytes, and immune transcriptional programs.
Caveat
The trial was short and small, and its primary findings were immune biomarkers in healthy adults rather than clinical aging or infection outcomes.
Simplified
Mitochondrial dysfunction and stem cell exhaustion contribute to age-related immune decline, yet clinical interventions targeting immune aging are lacking. Recently, we demonstrated that urolithin A (UA), a inducer, expands T memory stem cells (T) and naive T cells in mice. In this randomized, double-blind, placebo-controlled trial, 50 healthy middle-aged adults received oral UA (1,000 mg day) or placebo for 4 weeks; time points of analysis were baseline and day 28. Primary outcomes were phenotypical changes in peripheral CD3T cell subsets and immune metabolic remodeling. UA expanded peripheral naive-like, less terminally exhausted CD8cells (treatment difference 0.50 percentage points; 95% CI = 0.16 to 0.83; P = 0.0437) while also increasing CD8fatty acid oxidation capacity (treatment difference = 14.72 percentage points; 95% confidence interval (CI) = 6.46 to 22.99; P = 0.0061). Secondary outcomes included changes in plasma cytokine levels (IL-6, TNF, IL-1β, IL-10), immune populations assessed via flow cytometry, immune cell function, and mitochondrial content. Analysis revealed augmented mitochondrial biogenesis in CD8cells, increased peripheral CD56CD16NK cells, and nonclassical CD14CD16monocytes in UA-treated participants, as well as improved activation-elicited TNF secretion in T cells and bacterial uptake by monocytes. Exploratory single-cell RNA sequencing demonstrated UA-driven transcriptional shifts across immune populations, modulating pathways linked to inflammation and metabolism. These findings indicate that short-term UA supplementation modulates human immune cell composition and function, supporting its potential to counteract age-related immune decline and . ClinicalTrials.gov registration number: NCT05735886 . SCM -1 + + + + dim bright lo hi
Key numbers
0.50 percentage points
Increase in
Change in percentage of naive-like after 28 days of intake.
14.72 percentage points
Increase in CD8 T Cell Fatty Acid Oxidation Capacity
Change in fatty acid oxidation capacity of after supplementation.
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