EIF5A and Polyamines are required for fasting-mediated autophagy and longevity(Seminar-1), Autophagy as a pathway to rejuvenate immune responses(Seminar-2)



開催日時 2024/08/20 (Tuesday) 16:00~ 18:00
開催場所 Auditorium
演者 Dr. Sebastian Hofer(Seminar-1), Dr. Ghada Alsaleh(Seminar-2)
所属・職名 Max Delbrück Center (MDC) for Molecular Medicine in the Helmholtz Association _Postdoctoral Fellow, Simon Lab (https://www.mdc-berlin.de/simon)(Seminar-1), Botnar Institute for Musculoskeletal Sciences, University of Oxford _Principal Investigator and the Leader of the first UK Space Innovation Lab (https://www.ndorms.ox.ac.uk/team/ghada-alsaleh)(Seminar-2)
国名 Berlin, Germany(Seminar-1), Oxford, UK(Seminar-2)
演題 EIF5A and Polyamines are required for fasting-mediated autophagy and longevity(Seminar-1), Autophagy as a pathway to rejuvenate immune responses(Seminar-2)
使用言語 English
世話人 Division of Malaria Immunology 
Professor Cevayir Coban


Polyamine metabolism is embedded in critical metabolic processes, including one-carbon, arginine, and methionine metabolism, as well as the urea cycle. It is crucial for cellular growth, autophagy regulation, and cell survival. How these processes impact each other remains insufficiently understood. Importantly, polyamines decline during aging, which is causally linked to impaired autophagy regulation in aged cells.
We found that polyamines increase in fasting organisms and the knockout of the key enzyme ornithine decarboxylase (ODC1) impairs metabolic and proteomic starvation responses. We could show that ODC1 is essential for proper autophagy induction during starvation in yeast, worms and human cell lines. We further identified the unique spermidine-dependent hypusination activation of eIF5A as a critical event during the cellular adaptation to starvation. Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms in an autophagy-dependent manner. In line, we could show that polyamine biosynthesis is crucial for the health- and lifespan-promoting effects of intermittent fasting on survival and healthspan of yeast, flies, nematodes and mice.
Overall, our results hint at a previously unrecognized, yet essential, and conserved role of the polyamine pathway in the adaptation of organisms to fasting.

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 found that autophagy declines with age in human peripheral blood mononuclear cells. However, this decline can be reversed by spermidine, a natural polyamine, which restores a more youthful phenotype in 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.