Tier 3 — preclinical

Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses

Ghada Alsaleh, Isabel Panse, Leo Swadling, Hanlin Zhang, Felix Clemens Richter, Alain Meyer, Janet Lord, Eleanor Barnes, Paul Klenerman, Christopher Green, Anna Katharina Simon

eLife 2020 9:e57950

Bibliography

PubMed: PMID 33317695
PubMed Central: PMC7744099
DOI: 10.7554/eLife.57950
Trial registry: View on ClinicalTrials.gov Registered trial — results not yet published in a peer-reviewed journal.

Study snapshot

Design	Human vaccine cohort analyses plus ex-vivo mechanistic experiments
Model	Healthy vaccinees and T cells from younger and older human donors
Sample	Multiple human vaccine/T-cell cohorts and ex-vivo experiments
Intervention	Vaccination in underlying human cohorts; ex-vivo spermidine supplementation of T cells
Duration	Vaccine-response and ex-vivo experimental time courses; varies by cohort and assay
Endpoints	T-cell autophagy; IFN-gamma response; Vaccine response; eIF5A; TFEB; Age-related T-cell function

What the study showed, in plain terms

Older human T cells had lower spermidine and autophagy, and ex-vivo spermidine restored autophagy and aspects of function. In vaccinees, autophagy correlated with antigen-specific responses.

Key findings

The study is important mechanistic human evidence linking endogenous spermidine, autophagy and immune function, but it did not test oral spermidine capsules for vaccine efficacy.

What this study can and cannot tell us

Human causal work was ex vivo, and vaccine-response observations came from underlying vaccine cohorts. It cannot establish an oral dose-response or prove clinical vaccine benefit from supplementation.

Editorial review

Reviewed by the Biohack Blueprint research team

Khaled Mahmoud