Helmholtz Gemeinschaft


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

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplemental Information)

Item Type:Article
Title:Polyamines control eIF5A hypusination, TFEB translation, and autophagy to reverse B cell senescence
Creators Name:Zhang, H. and Alsaleh, G. and Feltham, J. and Sun, Y. and Napolitano, G. and Riffelmacher, T. and Charles, P. and Frau, L. and Hublitz, P. and Yu, Z. and Mohammed, S. and Ballabio, A. and Balabanov, S. and Mellor, J. and Simon, A.K.
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.
Keywords:Spermidine, eIF5A, TFEB, Autophagy, B Cell, Aaging, Animals, Mice
Source:Molecular Cell
Publisher:Cell Press
Page Range:110-125
Date:3 October 2019
Official Publication:https://doi.org/10.1016/j.molcel.2019.08.005
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library