Spermidine and Vaccinations

*This is a summary of the findings from various studies and articles. Further information and details on this study are located in the link below.*

The successful vaccination of the elderly against pathogens is considered one of the big challenges in our society. Immunosenescence, which is characterized by poor induction and recall of B and T memory responses upon exposure to new antigens, can lead to reduced immune responses following immunization of older adults. While most vaccines are less immunogenic and effective in the older population, little is known about the molecular mechanisms that underpin immune senescence. 

Autophagy is thought to be one of the few cellular processes that underlie many facets of cellular ageing including immune senescence. Autophagy limits mitochondrial dysfunction and accumulation of reactive oxygen species (ROS). Autophagy degrades protein aggregates that accumulate with age and its age-related decline could contribute to “inflammaging”, the age-related increase in inflammatory cytokines in blood and tissue. Loss of autophagy strongly promotes production of inflammatory cytokines. We previously found autophagy levels decline with age in human peripheral T cells. In addition, we find in autophagy-deficient immune cells the same cellular phenotype that cells display in older organisms; they accumulate ROS and damaged mitochondria.

It was shown in yeast and other model organisms that spermidine extends life-span via increased autophagy. 

We find that spermidine levels decline in peripheral blood mononuclear cells (PBMCs) in older humans; PBMCs give selective responses to the immune system and are the major cells in the human body immunity. This confirms earlier study in plasma in which spermidine levels were found to be low in the >65 age group and rising again in centenarians 35. Studies of this kind usually indicate that the phenotype is maladaptive with age as centenarians do not display many of the aging features of the age group below. However, the reasons for the age-related decline in spermidine in blood cells are not clear, and currently under investigation. Overall it is evident that endogenous spermidine maintains autophagy in human T cells.

This study demonstrates that the function of human T cells can be improved with spermidine. Taken together with our previous work on B cells, this leads us to the hypothesis that both T and B cell responses to infections and vaccinations are exquisitely reliant on sufficient autophagy levels, which are maintained by intracellular spermidine. This work highlights the potential of spermidine as a vaccine adjuvant in the older adults.

Ghada Alsaleh, Isabel Panse, Leo Swadling, et al. “Autophagy in T cells from aged donors is maintained by spermidine, and correlates with function and vaccine responses,” online: https://www.biorxiv.org/content/10.1101/2020.06.01.127514v1.full 

  • Don Moxley - Director of Applied Science

    Don Moxley is the Director of Applied Science at Longevity Labs. Moxley draws upon his career as an athlete, a sports scientist, and an instructor to lead and educate on the science of autophagy and longevity.