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Researchers at the Kennedy Institute identify a molecular pathway to boost vaccine responses in the elderly.

A new study by Professor Katja Simon and colleagues published in Molecular Cell shows that spermidine, a naturally occurring metabolite found in most human cell types, boosts antibody production in both old mice and immune cells from the elderly. The findings may offer an approach for improved vaccination strategies for older people who are less responsive to vaccines and more vulnerable to infection.

The team found that spermidine kick-starts the immune system through autophagy, a cellular recycling pathway that declines as cells age.

Katja explains "Our data reveal a novel molecular pathway where spermidine adds an essential modification to the protein, eIFA5, which is needed to produce the molecule TFEB, a master regulator of autophagy".

The authors have previously shown that spermidine targets autophagy to restore the function of old T cells in the immune system. The new work demonstrates a broader role for spermidine in rejuvenating the immune system which includes long-lived B cell responses, the main correlate of protection offered by vaccines. These data add to growing evidence from mice that spermidine protects against a range of age-associated defects, including cardiovascular disease and cognitive decline, by stabilising autophagy.

"Spermidine levels and autophagy are both known to decline with age. Our work links these two observations and explains why cellular autophagy declines with age and the downstream effect in ageing tissues. The data reveals multiple promising targets to restore autophagy levels and tissue functions in the elderly, to treat age-related disease" says Katja.

The research was funded by the Wellcome Trust, China Scholarship Council and Elysium Health.

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