Published in the journal Aging Cell, the findings point to spermidine — a compound found in nature — as a substance that may bolster how the immune systems of certain older adults respond to vaccination, with the proposed mechanism involving a reduction in biological markers associated with immune ageing.
Across the lifespan, the body's defences gradually lose their capacity to neutralise infections and mount a full response to vaccination. Referred to in medical literature as immunosenescence, this age-linked deterioration of immune function can leave certain older adults with reduced defence against both age-related conditions and the full protective benefit of vaccines.
Two researchers jointly steered the project: Dr. Katja Simon, who holds a Group Leader position within the Cell Biology of Immunity lab at the Max Delbrück Center, and Dr. Ghada Alsaleh, an Associate Professor attached to the Nuffield Department of Orthopaedics, Rheumatology & Musculoskeletal Sciences at the University of Oxford, known as NDORMS.
The data from that research pointed to measurable gains across multiple markers of immune function when participants received a daily spermidine supplement alongside COVID-19 vaccination.
Human cells generate spermidine on their own, and the compound turns up as well in a range of everyday foods — wheat germ, mushrooms, parmesan, and cheddar among them. Prior studies have pointed to the molecule's potential role in sustaining cellular upkeep processes that tend to diminish as the body ages, while Alsaleh notes that although a number of older patients build robust immunity following vaccination, others fail to generate adequate protection even across multiple doses.
Age-related changes in how immune cells function have been identified as a possible factor behind the pattern. The research team — which drew in contributors from the Oxford Vaccine Group, among them several doctoral-level scientists — noted in its data that spermidine may hold the capacity to partially rehabilitate immune-system performance within that population. Among those involved were Paul Klenerman, Teresa Lambe, and Lucy Jones, with Owen B. Spiller contributing from Cardiff University.
Data gathered across the COVID-19 outbreak indicated that vaccines played a measurable role in reducing both hospitalisation rates and fatalities among those who contracted the virus. Protective antibodies and T cells tend to form in smaller numbers among older adults following vaccination. Flu vaccination has shown comparable trends in the data gathered so far.
A cohort of 40 adults aged 65 and older, all in good health, was brought into the study so researchers could test whether spermidine had any effect on that response. For 13 weeks following their third COVID-19 vaccination, each study participant consumed either a six-milligram daily dose of spermidine or a placebo.
Roughly a quarter of those enrolled in the study mounted only faint antibody responses, even when their vaccination course had extended to three doses. Elevated DNA damage and molecular indicators of cellular senescence were both present in the immune cells, pointing to measurable acceleration in the biological ageing process. Cells that have sustained damage or reached the end of their functional lifespan can enter a state where they halt normal activity yet persist within the body, building up in number as time passes.
Spermidine recipients who had not mounted a response to vaccination showed measurable gains across several markers tied to immune protection from that vaccine. Antibody levels against SARS-CoV-2 tended to climb higher among those participants, and their blood samples mounted a more robust neutralising response across multiple viral variants.
Elevated autophagy activity and a reduction in biomarkers tied to immune system ageing were among the additional outcomes the team attributed to spermidine. Within cells, a built-in housekeeping mechanism identifies and breaks down worn or faulty components, keeping the cell's internal machinery running as it should.
No adverse effects were noted, and participants appeared to handle the supplement without difficulty. No harmful effects turned up in the data when researchers examined outcomes linked to the treatment.
The trial enrolled only 40 participants, a number the researchers themselves acknowledged as modest, and Simon noted that the work was structured as a pilot rather than a confirmatory study — meaning broader investigations across larger groups, and across other vaccines including seasonal influenza formulations, would be needed before any consistent effect of spermidine on immune responses to vaccination could be established with confidence.
