bims-hypusi 2026-02-08 papers

Issue of 2026–02–08
two papers selected by
Sebastian J. Hofer, Max Delbrück Center

Amino Acids. 2026 Feb 02.

Epithelial hypusination regulates Helicobacter pylori-induced gastric inflammation.

Alain P Gobert, Kara M McNamara, Caroline V Hawkins, Mohammad Asim, Daniel P Barry, Alberto G Delgado, Kristie L Rose, Purvi Patel, Regina N Tyree, Kate S Carson, Lori A Coburn, M Blanca Piazuelo, Keith T Wilson.

Hypusine is a unique amino acid synthesized on the eukaryotic initiation factor 5 A (EIF5A) from the polyamine spermidine by deoxyhypusine synthase (DHPS). Hypusination of EIF5A plays a key role in translation. Here, we examined the contribution of the epithelial hypusination pathway to gastric inflammation induced by Helicobacter pylori. Immunohistochemical analyses revealed increased expression of DHPS and hypusinated EIF5A (EIF5AHyp) in the gastric mucosa of patients with H. pylori gastritis compared to uninfected individuals, notably within gastric epithelial cells (GECs) and immune infiltrates. Then, we created a mouse model with epithelial-specific deletion of Dhps (DhpsΔepi) and confirmed the reduction of DHPS and EIF5AHyp in GECs. H. pylori-infected DhpsΔepi mice exhibited an attenuation of gastric histologic inflammation scores compared with infected Dhpsfl/+ controls, without alteration in bacterial colonization levels. Quantitative proteomics of isolated GECs showed that Dhps deletion altered the expression of proteins involved in organismal injury, cancer, and gastrointestinal diseases in naïve mice. Upon H. pylori infection, inflammatory and immune response proteins, including signaling factors and immunoglobulin mediators, were less induced in DhpsΔepi GECs, and pathways linked to tissue injury and inflammation were selectively downregulated. Together, these findings demonstrate that epithelial hypusination supports H. pylori-driven gastric inflammation without affecting bacterial persistence. Targeting DHPS-dependent EIF5A hypusination may thus represent a novel therapeutic strategy to limit H. pylori-associated mucosal injury and disease progression.

Keywords: Gastritis; Hypusine; Infection; Polyamines; Proteome

DOI: https://doi.org/10.1007/s00726-026-03496-3

Amino Acids. 2026 Jan 31. 58(1): 7

Polyamine metabolism as a regulator of cellular and organismal aging.

Takeshi Uemura, Jun Takayama, Akihiro Oguro, Yusuke Terui.

Polyamines - putrescine, spermidine, and spermine - are ubiquitous cationic molecules that are essential for cellular proliferation and homeostasis. Their intracellular concentrations decline with age, contributing to physiological and cognitive deterioration. Recent studies have revealed that spermidine supplementation extends lifespan and improves cognitive and cardiac function in various model organisms, suggesting that maintaining polyamine balance has anti-aging potential. Polyamine metabolism is tightly regulated through biosynthesis, degradation, and transport; however, age-associated upregulation of spermine oxidase (SMOX) and accumulation of its toxic byproduct acrolein promote oxidative damage and cellular senescence. Suppressing SMOX activity or polyamine degradation attenuates senescence markers and DNA damage, highlighting spermine catabolism as a therapeutic target. Polyamines also modulate epigenetic regulation, including DNA methylation and histone acetylation, thereby influencing gene expression and chromatin structure during aging. Moreover, polyamine-dependent hypusination of eIF5A sustains protein synthesis in senescent cells. These multifaceted actions indicate that polyamine metabolism integrates redox control, translational regulation, epigenetic maintenance and autophagy to determine cellular and organismal longevity. While animal studies demonstrate clear anti-aging effects of spermidine and spermine, human clinical evidence remains limited, with variable outcomes likely due to bioavailability and metabolic conversion. Future strategies combining dietary or probiotic polyamine enhancement, enzyme-targeted inhibitors, and personalized metabolic interventions hold promise for extending healthspan. Collectively, maintaining optimal polyamine homeostasis emerges as a key approach to counteract aging and age-related diseases.

Keywords: Aging; Autophagy; Epigenetic regulation; Polyamine metabolism; Senescence; Spermine oxidase; Translational regulation

DOI: https://doi.org/10.1007/s00726-026-03497-2