Tier 2 — strong

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

Alsaleh G, Ali M, Kayvanjoo AH, Liu F, Moreau T, Bibi S, Luo L, Govender M, Carroll M, Hofer SJ, Eisenberg T, Magnes C, Simon AK, et al.

Aging Cell 2026 25(6):e70545

Bibliography

PubMed: PMID 42169618
PubMed Central: PMC13240347
DOI: 10.1111/acel.70545
Funding: Supported by Arthritis UK, Wellcome Investigator Award, UK SPINE, TLL The Longevity Labs GmbH and Helmholtz Association, University of Graz, and Austrian Science Fund grants, as disclosed in the paper.
Competing interests: A.K. Simon and Tobias Eisenberg disclosed consultancy relationships with TLL The Longevity Labs GmbH; G. Alsaleh and A.K. Simon disclosed consultancy relationships with Oxford Healthspan. The paper states TLL had no input into trial design, results, analysis or manuscript.

Study snapshot

Design	Double-blind randomized placebo-controlled pilot trial
Model	Adults older than 65 years following a third SARS-CoV-2 vaccine dose
Sample	40 participants
Intervention	Oral spermidine 6 mg/day versus placebo
Duration	13 weeks
Endpoints	Tolerability; Immune-senescence markers; Spike-specific IgG secretion; Memory B-cell recall; Neutralizing antibody activity; Autophagy-related gene expression

What the study showed, in plain terms

In this 2026 pilot trial, adults over 65 took 6 mg/day of spermidine or placebo for 13 weeks after COVID-19 vaccination. The supplement was well tolerated. Among participants who had initially responded poorly to vaccination, spermidine improved several immune-response measures and shifted immune-senescence and autophagy markers in a favorable direction.

Key findings

Daily 6 mg spermidine for 13 weeks was well tolerated in the older-adult study population.
In vaccine non-responders, spermidine significantly improved spike-specific IgG secretion, memory B-cell recall responses and neutralizing antibody activity.
Immune-senescence markers and B-cell autophagy-related signatures shifted in a direction consistent with improved cellular maintenance.

What this study can and cannot tell us

This was a small pilot study of 40 older adults in a specific post-vaccination setting. The strongest immune benefits were reported in vaccine non-responders, so the findings should not be generalized to younger adults, all immune outcomes, or lifespan extension. Larger independent trials are needed.

Editorial review

Reviewed by the Biohack Blueprint research team

Khaled Mahmoud