Authors
Jun Wang, Yu Wang, Koki Ichimaru, Maharani Aprilia, Yasuharu Haku, Jiaxin Gu, Mai Kiyono, Keiko Yurimoto, Tomonori Yaguchi, Tasuku Honjo, Koji Kitaoka, Kenji Chamoto
Published in
International immunology. Oct 30, 2026. Epub Oct 30, 2026.
Abstract
Spermidine (SPD) is a polyamine metabolite with anti-aging and immunomodulatory properties. We previously reported that SPD enhances mitochondrial respiration in CD44- CD8+ naïve T cells through the upregulation of fatty acid oxidation (FAO). However, the effects of SPD on CD44+ CD8+ effector T cells remain unknown. We found that SPD suppressed mitochondrial oxygen consumption rate (OCR) in CD44+ CD8+ T cells from aged mice, in contrast to its effects on those from young mice. This FAO-dependent reduction in respiration was associated with mitochondrial oxidative stress and accompanied by reduced IFN-γ production and proliferative capacity. Notably, within the aged CD44+ CD8+ T cell compartment, senescence-like CD44+ CD49d- subset (CD49d- cells)-predominantly accumulated with age-exhibited a marked decrease in OCR following SPD treatment, whereas CD44+ CD49d+ CD8+ T cells (CD49d+ cells) were unaffected. In CD49d- cells, SPD treatment disrupted redox balance as evidenced by reduced intracellular reduced-thiol levels with unchanged mitochondrial reactive oxygen species (ROS) levels, suggesting consumption of antioxidant reserves. SPD also induced structural remodeling of mitochondria in CD49d- cells, characterized by a shift toward shorter, more fragmented mitochondria with wider cristae spacing than in CD49d+ cells. In summary, our findings reveal that SPD paradoxically compromises mitochondrial respiration in a specific subset of aged CD8+ T cells by perturbing fatty acid metabolism and redox homeostasis.
PMID:
42958929
Bibliographic data and abstract were imported from PubMed on 30 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 3
- Comments 0