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As we age, the immune system gradually declines and becomes less effective at responding to infections and vaccines. This process, known as immunosenescence, contributes to the increased risk of age-related health issues in older people and can weaken the response to vaccinations.
During the COVID-19 pandemic, over 92% of COVID-related deaths occurred in people over 60. In addition, vaccination is crucial in reducing severe illness and death, but older adults often produced lower levels of protective antibodies and T-cell responses following vaccination, for example against influenza, limiting vaccine effectiveness compared with younger populations.
Researchers from NDORMS, led by Professor Katja Simon and Associate Professor Ghada Alsaleh, set out to explore whether immune function, and therefore vaccine response, in older adults could be improved with daily spermidine supplements.
Spermidine is a naturally occurring molecule made by our cells, but it is also found in foods such as wheat germ, mushrooms and some cheeses, and previous studies have suggested it can support cellular maintenance processes that decline with age.
The findings, published in Aging Cell, come from a pilot clinical trial involving adults aged over 65 who had received three doses of a COVID-19 vaccine.
The double-blind, randomised, placebo-controlled trial enrolled 40 healthy adults aged over 65. Participants received either a daily spermidine supplement or a placebo for 13 weeks following their third COVID-19 vaccination.
The supplement was found to be safe and well tolerated, with no adverse effects linked to treatment.
The findings showed that around one quarter of participants showed very weak antibody responses despite having received three vaccine doses. These individuals had immune cells with clear signs of biological ageing, including increased DNA damage and markers associated with cellular senescence.
Among these vaccine non-responders, spermidine supplementation was associated with a substantial improvement in several measures of vaccine immunity. Participants showed increased levels of antibodies against SARS-CoV-2 through stronger B-cell responses, and improved neutralising activity against multiple viral variants.
The team found that spermidine appeared to reduce markers of immunosenescence, and stimulate autophagy, a natural cellular recycling process that helps cells remove damaged components and maintain healthy function.
Ghada said: 'Many older adults respond well to vaccines, but some do not develop strong protection even after repeated vaccination. Our study suggests that biological ageing of immune cells may be one reason why this happens, and that spermidine could help restore aspects of immune function in this group. Our findings could potentially be used to identify people at risk of poor vaccine responses, while interventions that target these ageing processes may help improve protection in later life.'
Katja added: 'The study was designed as a pilot trial and involved a relatively small number of participants. Larger studies will be needed to determine whether spermidine can consistently improve vaccine responses and whether similar effects are seen with other vaccines, such as those used against seasonal influenza.'
The study was a collaboration between the Kennedy Institute, the Oxford Vaccine Group, and Cardiff University. It was supported by Arthritis UK and the Wellcome Trust.