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| Item Type: | Article |
|---|---|
| Title: | Spermidine mitigates immune cell senescence and boosts vaccine responses in healthy older adults -- a pilot study |
| Creators: |
Alsaleh, Ghada, Ali, Mohammad  ORCID: https://orcid.org/0000-0003-0170-7182, Kayvanjoo, Amir Hossein ORCID: https://orcid.org/0000-0003-1315-8336, Liu, Feng, Moreau, Tanaïs, Bibi, Sagida, Luo, Lin, Govender, Melissa, Carroll, Miles, Hofer, Sebastian J., Tobias, Eisenberg, Magnes, Christoph, Kell, Loren ORCID: https://orcid.org/0000-0003-1322-2027, Chung, Christopher, Deng, Yu, Bhandari, Aneesha, Garner, Lucy ORCID: https://orcid.org/0000-0002-6461-252X, Conrad, Thomas ORCID: https://orcid.org/0000-0001-5618-6295, Chen, Liye, Kronsteiner-Dobramysl, Barbara, Dunachie, Susie, Spiller, Owen B. ORCID: https://orcid.org/0000-0002-9117-6911, Lambe, Teresa, Klenerman, Paul, Jones, Lucy C. and Simon, A. Katharina ORCID: https://orcid.org/0000-0002-4077-7995
|
| Abstract: | Older adults are highly vulnerable to infectious diseases, and vaccines are often less effective in this population because of diminished B and T cell memory responses driven by impaired autophagy, immunosenescence, and chronic low-grade inflammation. Spermidine has been shown to counteract immunosenescence and induce autophagy in preclinical models, and its levels decline with age in humans. We conducted a double-blind, randomised, placebo-controlled pilot study in 40 adults over 65 years of age following their third SARS-CoV-2 vaccine dose to assess the safety of Spermidine and its effects on vaccine-induced immunity. Daily oral supplementation (6 mg, 13 weeks) was well-tolerated. Vaccine non-responsiveness was common, and non-responders exhibited a distinct immune-senescence signature marked by elevated p16, mTOR signalling, and γ-H2AX+ DNA damage in lymphocytes. Spermidine reversed these features and significantly enhanced spike-specific IgG secretion, memory B cell recall responses and neutralising antibody activity, specifically in non-responders. Single-cell RNA-seq after treatment revealed increased expression of TFEB targets and autophagy-related genes in B cells, in line with elevated autophagic flux. These findings suggest that targeting immune cell senescence with Spermidine may improve vaccine responsiveness in older adults and highlight immune-senescence markers as potential predictors of vaccine failure in ageing populations. |
| Keywords: | Autophagy, B-Lymphocytes, COVID-19, COVID-19 Vaccines, Cellular Senescence, Double-Blind Method, Immunosenescence, Pilot Projects, SARS-CoV-2, Spermidine |
| Source: | Aging Cell |
| ISSN: | 1474-9718 |
| Publisher: | Wiley |
| Volume: | 25 |
| Number: | 6 |
| Page Range: | e70545 |
| Date: | June 2026 |
| Official Publication: | https://doi.org/10.1111/acel.70545 |
| PubMed: | View item in PubMed |
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