Autophagy in T cells maintained by spermidine

New preliminary study demonstrates spermidine maintains autophagy in T cells and may improve vaccine protection in older adults.

Spermidine, a polyamine that boosts the removal of cellular debris in immune cells, and which is available as a supplement, may increase the protective effects of vaccines in older adults, a preliminary study published today in eLife shows. Spermidine was was first isolated from semen, which explains its name.

Longevity.Technology: Spermidine is important for cell growth and maintaining genetic stability and increased spermidine levels have been found to lessen the risk of cardiovascular diseases and the likelihood of developing cancer. However, spermidine levels in the body decrease as we age. This new study indicates that spermidine could have another Longevity benefit, maintaining autophagy, a vital homeostatic process, while also making vaccines more effective. 

Spermidine has previously been linked with autophagy [1], a cytoprotective process that clears cellular damage, recycles important molecules and balances sources of energy at critical times in development. Linked to nutrient stress, autophagy plays a key role in in the mechanism that extends lifespan through calorie restriction.

The results from the new study show that spermidine’s role in maintaining autophagy in T cells may further immunity research and lead to new approaches to protect older individuals from viruses such as the one causing the current COVID-19 pandemic and influenza.

“Our findings will inform vaccine trials in which autophagy-boosting agents, such as spermidine, are given in a controlled environment to older participants,”

“Older adults are at high risk of being severely affected by infectious diseases, but unfortunately most vaccines in this age group are less efficient than in younger adults,” explains lead author Ghada Alsaleh, a postdoctoral researcher at the Kennedy Institute of Rheumatology, University of Oxford, UK.

Previously, Alsaleh and colleagues showed that immune cells in older mice may become less efficient at autophagy, and this leads to a poorer immune response in the animals. In the current study, they looked at samples from young and old people participating in clinical trials for vaccines against the respiratory syncytial virus and the hepatitis C virus to see if the same event happens in human immune cells called T cells. They found that autophagy increases in T cells from younger people after receiving vaccines, but this response is blunted in older people.

When they examined T cells from the older individuals in the laboratory, the team found that these cells have less of a natural compound called spermidine. Spermidine ramps up autophagy and boosts T-cell function. Supplementing these older immune cells with spermidine in the laboratory restored autophagy to the same levels seen in T cells from younger people. “Our work suggests that boosting autophagy during vaccination may help make vaccines more effective for older people,” Alsaleh says.

A small clinical trial recently tested whether giving spermidine to older adults would improve their cognitive function. As the results were positive, and spermidine did not appear to have any harmful effects, this provides some evidence that it would be safe to test whether spermidine might also be helpful for boosting the immune response of older people to vaccines.

“Our findings will inform vaccine trials in which autophagy-boosting agents, such as spermidine, are given in a controlled environment to older participants,” concludes senior author Anna Katharina Simon, Professor of Immunology at the University of Oxford. “It will be interesting to see whether these agents can enhance vaccination efficiency and help protect older people from viral infections.”


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