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Start Over Author "Mellor, Jane" Journal molecular cell
11 results on '"Mellor, Jane"'

2. Polyamines control eIF5A hypusination, TFEB translation, and autophagy to reverse B cell senescence

Author

Zhang, Hanlin, Alsaleh, Ghada, Feltham, Jack, Sun, Yizhe, Napolitano, Gennaro, Riffelmacher, Thomas, Charles, Philip, Frau, Lisa, Hublitz, Philip, Yu, Zhanru, Mohammed, Shabaz, Ballabio, Andrea, Balabanov, Stefan, Mellor, Jane, Simon, Anna Katharina, University of Zurich, Simon, Anna Katharina, Zhang, Hanlin, Alsaleh, Ghada, Feltham, Jack, Sun, Yizhe, Napolitano, Gennaro, Riffelmacher, Thoma, Charles, Philip, Frau, Lisa, Hublitz, Philip, Yu, Zhanru, Mohammed, Shabaz, Ballabio, Andrea, Balabanov, Stefan, and Mellor, Jane

Subjects
1307 Cell Biology, B cell, TFEB, autophagy, Cancer Research, aging, spermidine, 10032 Clinic for Oncology and Hematology, 1312 Molecular Biology, 610 Medicine & health, eIF5A
Abstract

Failure to make adaptive immune responses is a hallmark of aging. Reduced B cell function leads to poor vaccination efficacy and a high prevalence of infections in the elderly. Here we show that reduced autophagy is a central molecular mechanism underlying immune senescence. Autophagy levels are specifically reduced in mature lymphocytes, leading to compromised memory B cell responses in old individuals. Spermidine, an endogenous polyamine metabolite, induces autophagy in vivo and rejuvenates memory B cell responses. Mechanistically, spermidine post-translationally modifies the translation factor eIF5A, which is essential for the synthesis of the autophagy transcription factor TFEB. Spermidine is depleted in the elderly, leading to reduced TFEB expression and autophagy. Spermidine supplementation restored this pathway and improved the responses of old human B cells. Taken together, our results reveal an unexpected autophagy regulatory mechanism mediated by eIF5A at the translational level, which can be harnessed to reverse immune senescence in humans.

Published
2019

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