Aging cellMay 22, 2026

Spermidine Reduces Aging of Immune Cells and Improves Vaccine Response in Healthy Older Adults

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 28, 2026

Abstract

Essence

In this pilot trial, spermidine improved SARS-CoV-2 vaccine immune responses in older adults who had not responded to vaccination.

Evidence

A double-blind randomized placebo-controlled pilot study in 40 adults older than 65 found 13 weeks of oral spermidine was well tolerated and, in vaccine non-responders, increased spike-specific IgG secretion, memory B cell recall, neutralizing activity, and B-cell autophagy-related gene expression.

Caveat

The signal comes from a small short-term pilot study and the main immune benefits were specific to the non-responder subgroup rather than the whole cohort.

Simplified

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.