Abstract

The changes in the immune system that occur with age have been the subject of much research in the past few decades. They are believed to be a contributing factor to a range of health issues including cancer, autoimmune disorders, chronic inflammation, and poor responses to vaccines. In particular, the COVID-19 pandemic of 2020 highlighted the vulnerability of older adults to severe illness due to immune aging. We recently revealed the role of autophagy, the main cellular bulk degradation pathway, in immune aging. We have shown that TFEB, a master regulator of autophagy and lysosomal biogenesis level decrease with age in human peripheral blood mononuclear cells, and TFEB levels can be increased by spermidine (natural polyamine) to reverse the ageing phenotype of these cells. In addition, we conducted a feasibility study, phase1 double-blinded, randomised controlled trial to examine the safety of Spermidine supplements and its effects on the immune response (antibodies) to COVID vaccine in older people. Interestingly, our outcome of these study, showed that Spermidine has no associated safety concerns and could improve the long lasting immune responses to COVID vaccine in older people. With these findings we have provided evidence for the importance of spermidine in vaccine immunogenicity in older humans.