Spermidine mitigates immune cell senescence and boosts vaccine responses in healthy older adults - a pilot study

Alsaleh, Ghada, Ali, Mohammad, Kayvanjoo, Amir Hossein, Liu, Feng, Moreau, Tanais, Spiller, Owen B. ORCID: https://orcid.org/0000-0002-9117-6911 and Jones, Lucy C. ORCID: https://orcid.org/0000-0002-3872-4376 2026. Spermidine mitigates immune cell senescence and boosts vaccine responses in healthy older adults - a pilot study. Aging Cell 25 (6) , e70545. 10.1111/acel.70545

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (6MB) | Preview

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Wiley
ISSN:	1474-9718
Funders:	Arthritis UK grant (22617), Wellcome Investigator award (220784/Z/20/Z), UK SPINE, TLL The Longevity Labs GmbH and Helmholtz Association (REK-0157) and University of Graz and by the Austrian Science Fund (FWF) grants (P33957, TAI6021000)
Date of First Compliant Deposit:	26 May 2026
Date of Acceptance:	7 May 2026
Last Modified:	27 May 2026 14:09
URI:	https://orca.cardiff.ac.uk/id/eprint/187216

Actions (repository staff only)

Edit Item