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| Item Type: | Preprint |
|---|---|
| Title: | Spermidine mitigates immune cell senescence, enhances autophagy, and boosts vaccine responses in healthy older adults |
| Creators Name: | Alsaleh, Ghada, Ali, Mohammad, Kayvanjoo, Amir, Liu, Feng, Bibi, Sagida, Luo, Lin, Govender, Melissa, Carroll, Miles, Hofer, Sebastian, Eisenberg, Tobias, Magnes, Christoph, Kell, Loren, Chung, Christopher, Deng, Yu, Bhandari, Aneesha, Chen, Liye, Kronsteiner-Dobramysl, Barbara, Dunachie, Susie, Spiller, Owen, Lambe, Teresa, Klenerman, Paul, Jones, Lucy and Simon, Anna Katharina |
| Abstract: | Older adults are particularly vulnerable to infectious diseases, and vaccines are often less effective in this population due to immunosenescence, which is characterized by diminished B and T memory responses. Autophagy is believed to underlie many facets of cellular aging, including immunosenescence. It is crucial for maintaining memory T and B cell functions but declines with age, along with the endogenous metabolite spermidine that helps maintain autophagy levels. We conducted a double-blind, randomized, placebo-controlled study in 40 volunteers over 65, administering oral spermidine after their third SARS-CoV-2 vaccine dose. Spermidine reduced immune cell senescence, evidenced by decreased p16 expression in lymphocytes. Following spermidine treatment, autophagic ux, TFEB targets, and autophagy-related genes detected by scRNA-seq were highly enriched in B cells. Spermidine signi cantly increased spike-speci c IgG secretion and memory B cells, and neutralizing antibody activity against SARS-CoV-2 strains, in vaccine non-responders that also presented with high immune cell senescence. Targeting immune senescence using spermidine may offer a practical approach to improve immune responses in vaccine non-responders, as a post- or pre-vaccination intervention. Additionally, it highlights the utility of immune senescence markers as predictive biomarkers for identifying vaccine non-responders, addressing a key challenge in vaccine development for an aging population. |
| Source: | Research Square |
| Publisher: | Research Square |
| Article Number: | rs.3.rs-5686388 |
| Date: | 2 April 2025 |
| Official Publication: | https://doi.org/10.21203/rs.3.rs-5686388/v1 |
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