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Peer-reviewedCC BYAging Cell

Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study

  • Ghada Alsaleh1,2
  • Mohammad Ali3
  • Amir Hossein Kayvanjoo4
  • Feng Liu1
  • Tanaïs Moreau1
  • Sagida Bibi5
  • Lin Luo5,2
  • Melissa Govender6
  • Miles Carroll6
  • Sebastian J. Hofer4
  • Eisenberg Tobias7,8,9
  • Christoph Magnes10
14 more authors
  • Loren Kell1
  • Christopher Chung1
  • Yu Deng1
  • Aneesha Bhandari11
  • Lucy C. Garner11
  • Thomas Conrad4
  • Liye Chen1
  • Barbara Kronsteiner3
  • Dunachie Sj3
  • Owen Brad Spiller12
  • Teresa Lambe5
  • Paul Klenerman11
  • Lucy C. Jones12
  • A. Katharina Simon2,4
12 affiliations
  1. 1Botnar Institute for Musculoskeletal Sciences, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford Oxford UK
  2. 2Kennedy Institute of Rheumatology University of Oxford Oxford UK
  3. 3Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine University of Oxford Oxford UK
  4. 4Max‐Delbrück Center for Molecular Medicine in the Helmholtz Association Berlin Germany
  5. 5CAMS‐Oxford Institute, Nuffield Department of Medicine University of Oxford Oxford UK
  6. 6Centre for Human Genetics and the Pandemic Sciences Institute, Nuffield Department of Medicine University of Oxford Oxford UK
  7. 7BioTechMed Graz Graz Austria
  8. 8Field of Excellence BioHealth University of Graz Graz Austria
  9. 9Institute of Molecular Biosciences, NAWI Graz University of Graz Graz Austria
  10. 10HEALTH ‐ Institute for Biomedical Research and Technologies Joanneum Research Forschungsgesellschaft Graz Austria
  11. 11Centre for Global Health Research, Nuffield Department of Clinical Medicine University of Oxford Oxford UK
  12. 12Department of Microbiology, University Hospital of Wales, Heath Park Cardiff University Cardiff UK
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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.

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Cite

BibTeXRIS
BibTeX
@article{alsaleh2026spermidine,
  title = {{Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study}},
  author = {Ghada Alsaleh and Mohammad Ali and Amir Hossein Kayvanjoo and Feng Liu and Tanaïs Moreau and Sagida Bibi and Lin Luo and Melissa Govender and Miles Carroll and Sebastian J. Hofer and Eisenberg Tobias and Christoph Magnes and Loren Kell and Christopher Chung and Yu Deng and Aneesha Bhandari and Lucy C. Garner and Thomas Conrad and Liye Chen and Barbara Kronsteiner and Dunachie Sj and Owen Brad Spiller and Teresa Lambe and Paul Klenerman and Lucy C. Jones and A. Katharina Simon},
  journal = {Aging Cell},
  year = {2026},
  month = may,
  doi = {10.1111/acel.70545},
  url = {https://doi.org/10.1111/acel.70545},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Spermidine Mitigates Immune Cell Senescence and Boosts Vaccine Responses in Healthy Older Adults—A Pilot Study
AU  - Ghada Alsaleh
AU  - Mohammad Ali
AU  - Amir Hossein Kayvanjoo
AU  - Feng Liu
AU  - Tanaïs Moreau
AU  - Sagida Bibi
AU  - Lin Luo
AU  - Melissa Govender
AU  - Miles Carroll
AU  - Sebastian J. Hofer
AU  - Eisenberg Tobias
AU  - Christoph Magnes
AU  - Loren Kell
AU  - Christopher Chung
AU  - Yu Deng
AU  - Aneesha Bhandari
AU  - Lucy C. Garner
AU  - Thomas Conrad
AU  - Liye Chen
AU  - Barbara Kronsteiner
AU  - Dunachie Sj
AU  - Owen Brad Spiller
AU  - Teresa Lambe
AU  - Paul Klenerman
AU  - Lucy C. Jones
AU  - A. Katharina Simon
PY  - 2026
DA  - 2026/05/22
JO  - Aging Cell
DO  - 10.1111/acel.70545
UR  - https://doi.org/10.1111/acel.70545
AB  - 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.
SN  - 1474-9718
SN  - 1474-9726
SN  - 1474-9728
ER  -