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@ARTICLE{Denk:305613,
      author       = {D. Denk and A. Singh and H. G. Kasler and D. D'Amico and J.
                      Rey and L. Alcober-Boquet and J. M. Gorol and C. Steup and
                      R. Tiwari and R. Kwok and R. J. Argüello and J. Faitg and
                      K. Sprinzl and S. Zeuzem$^*$ and V. Nekljudova and S. Loibl
                      and E. Verdin and C. Rinsch and F. R. Greten$^*$},
      title        = {{E}ffect of the mitophagy inducer urolithin {A} on
                      age-related immune decline: a randomized, placebo-controlled
                      trial.},
      journal      = {Nature aging},
      volume       = {5},
      number       = {11},
      issn         = {2662-8465},
      address      = {London},
      publisher    = {Nature Research},
      reportid     = {DKFZ-2025-02263},
      pages        = {2309-2322},
      year         = {2025},
      note         = {2025 Nov;5(11):2309-2322},
      abstract     = {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 mitophagy inducer,
                      expands T memory stem cells (TSCM) 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-1) or placebo for 4 weeks; time points of analysis
                      were baseline and day 28. Primary outcomes were phenotypical
                      changes in peripheral CD3+ T cell subsets and immune
                      metabolic remodeling. UA expanded peripheral naive-like,
                      less terminally exhausted CD8+ cells (treatment difference
                      0.50 percentage points; $95\%$ CI = 0.16 to 0.83; P =
                      0.0437) while also increasing CD8+ fatty 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 CD8+ cells, increased
                      peripheral CD56dimCD16bright NK cells, and nonclassical
                      CD14loCD16hi monocytes 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 inflammaging.
                      ClinicalTrials.gov registration number: NCT05735886 .},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41174221},
      doi          = {10.1038/s43587-025-00996-x},
      url          = {https://inrepo02.dkfz.de/record/305613},
}