bims-polyam 2025-02-09 papers

Issue of 2025–02–09
three papers selected by
Sebastian J. Hofer, University of Graz

Physiol Rep. 2025 Feb;13(3): e70209

Effect of spermidine intake on overload-induced skeletal muscle hypertrophy in male mice.

Tomohiro Iwata, Takanaga Shirai, Riku Tanimura, Ryoto Iwai, Tohru Takemasa.

Skeletal muscles exhibit high plasticity, such as overload-induced hypertrophy or immobilization-induced atrophy. During sports, skeletal muscle hypertrophy is induced by training to improve performance. Spermidine is a type of polyamine and oral intake of spermidine exerts many beneficial effects on health through various mechanisms, such as promoting autophagy and improving mitochondrial function. In a recent study, we showed that spermidine intake activates mTOR signaling and significantly increases the mean fiber cross-sectional area (CSA) 14 days after injury. This suggests that spermidine promotes the anabolic growth of differentiated muscle (i.e., muscle hypertrophy); however, calorie restriction, which has been reported to have effects on the same molecular mechanisms as spermidine (promoting autophagy and improving mitochondrial function), promotes skeletal muscle regeneration, while inhibiting skeletal muscle hypertrophy. Therefore, we evaluated the effect of spermidine intake on skeletal muscle hypertrophy in mice using a synergistic ablation-induced muscle hypertrophy model. Our results showed that spermidine intake significantly decreased mean myofiber of CSA, but this was not consistent with the change in skeletal muscle wet weight. We also analyzed autophagy, mTOR signaling, inflammation, and mitochondria, but no significant effects of spermidine intake were observed at most protein expression levels. Therefore, spermidine intake does not affect overload-induced skeletal muscle hypertrophy, and even if it does, the effect is suppressive.

Keywords: autophagy; mTOR signaling; mitochondria; skeletal muscle hypertrophy; spermidine

DOI: https://doi.org/10.14814/phy2.70209

Clin Nutr. 2025 Jan 22. pii: S0261-5614(25)00026-3. [Epub ahead of print]46 80-87

Breastmilk polyamines modify gut gene expression in children at three months of age.

Nela Study Group

BACKGROUND & AIMS: Breastmilk is one of the main sources of exogenous polyamines for newborns and contains higher polyamine content than infant formulas. Polyamines are involved in gut maturation and immune system regulation in animals, although the underlying mechanisms are not fully understood. We quantified polyamines in human mature breastmilk and evaluate their effects on intestinal gene expression in babies at three months of age.
METHODS: Polyamines were quantified in mature milk of 195 women from the prospective Mediterranean NELA birth cohort (Murcia, Spain) at 3 months postpartum. Maternal dietary intake was assessed by food frequency questionnaires. Intestinal gene expression was analysed in babies receiving breastmilk, with high (>p50, n = 25) or low (<p50, n = 27) polyamine content, at 3 m of age, by microarray using a non-invasive method on gut exfoliated cells.
RESULTS: Spermidine and spermine were the most prevalent polyamines in breastmilk at 3 months postpartum, while levels of putrescine were lower. Maternal dietary intake of polyamines was not associated with polyamine concentration in breastmilk and there were no differences in the polyamine content between allergic and non-allergic mothers. Microarray analyses of exfoliated gut cells revealed that cell localization and immune system were the most significant biological processes affected by high vs low polyamines in breastmilk. There were 15 differentially expressed genes, 3 up-regulated and 12 down-regulated, in high compared to low polyamine groups. Among the up-regulated genes were tumour necrosis factor alpha-induced protein 6 (TNFAIP6) and interleukin 8; while other immune system-related genes, such as integral membrane protein 2C, lymphocyte antigen 6 complex, transmembrane protein 179B were down-regulated.
CONCLUSIONS: Mature breastmilk presents spermidine and spermine as the most prevalent polyamines. Babies receiving milk with higher polyamine levels showed differences in the expression of genes associated with cell localization and immune system processes.

Keywords: Breastmilk; Exfoliome; Gene expression; Intestine; Polyamines; Transcriptome

DOI: https://doi.org/10.1016/j.clnu.2025.01.025

J Biol Chem. 2025 Jan 31. pii: S0021-9258(25)00098-5. [Epub ahead of print] 108251

Polyamines enhance repeat-associated non-AUG translation from CCUG repeats by stabilizing the tertiary structure of RNA.

Akihiro Oguro, Takeshi Uemura, Kodai Machida, Kanata Kitajiri, Ayasa Tajima, Takemitsu Furuchi, Gota Kawai, Hiroaki Imataka.

Repeat expansion disorders are caused by abnormal expansion of microsatellite repeats. Repeat-associated non-AUG (RAN) translation is one of the pathogenic mechanisms underlying repeat expansion disorders, but the exact molecular mechanism underlying RAN translation remains unclear. Polyamines are ubiquitous biogenic amines that are essential for cell proliferation and cellular functions. They are predominantly found in cells in complexes with RNA and influence many cellular events, but the relationship between polyamines and RAN translation is yet to be explored. Here, we show that, in both a cell-free protein synthesis system and cell culture, polyamines promote RAN translation of RNA containing CCUG repeats. The CCUG-dependent RAN translation is suppressed when cells are depleted of polyamines but can be recovered by the addition of polyamines. Thermal stability analysis revealed that the tertiary structure of the CCUG-repeat RNA is stabilized by the polyamines. Spermine was the most effective polyamine for stabilizing CCUG-repeat RNA and enhancing RAN translation. These results suggest that polyamines, particularly spermine, modulate RAN translation of CCUG-repeat RNA by stabilizing the tertiary structure of the repeat RNA.

Keywords: RAN translation; RNA structure; cell-free protein synthesis system; neurodegenerative disease; polyamine; repeat expansion disorder; spermine

DOI: https://doi.org/10.1016/j.jbc.2025.108251