Skip to Content
Merck
  • Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence.

Polyamines Control eIF5A Hypusination, TFEB Translation, and Autophagy to Reverse B Cell Senescence.

Molecular cell (2019-09-03)
Hanlin Zhang, Ghada Alsaleh, Jack Feltham, Yizhe Sun, Gennaro Napolitano, Thomas Riffelmacher, Philip Charles, Lisa Frau, Philip Hublitz, Zhanru Yu, Shabaz Mohammed, Andrea Ballabio, Stefan Balabanov, Jane Mellor, Anna Katharina Simon
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MISSION® esiRNA, targeting human EIF5A
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine and sodium bicarbonate. Without arginine, leucine, lysine, and phenol red, liquid, sterile-filtered, suitable for cell culture, designed for isotope labeling for cell culture applications
Sigma-Aldrich
Cycloheximide, Biotechnology Performance Certified
Sigma-Aldrich
1,7-Diaminoheptane, 98%
Sigma-Aldrich
Phosphatase substrate, 5 mg tablets
Sigma-Aldrich
Glass beads, acid-washed, 425-600 μm (30-40 U.S. sieve)
Millipore
Streptavidin−Agarose from Streptomyces avidinii, buffered aqueous suspension
Sigma-Aldrich
RPMI-1640 Medium, Modified, with sodium bicarbonate, without methionine, cystine and L-glutamine, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Mouse IgM ELISA Kit
Sigma-Aldrich
MISSION® 3X LacO Inducible Non-Target shRNA Control Plasmid DNA, Does not target any known genes
Sigma-Aldrich
p-Nitrophenyl Phosphate Liquid Substrate System, liquid
Sigma-Aldrich
Thapsigargin, ≥98% (HPLC), solid film
Sigma-Aldrich
4-Hydroxytamoxifen, ≥70% Z isomer (remainder primarily E-isomer)
Sigma-Aldrich
Tetraethylammonium borohydride, technical, ≥95% (T)