Polyamines as Universal Bioregulators across Kingdoms and Their role in Cellular Longevity and Death

Abstract

Polyamines (PAs) are important molecules that determine cell longevity or death. Studies have shown that nutritional supplementation with spermidine can reduce age-related pathology and increase life span in a number of organisms, including humans. In addition, applying PAs to plants prevents their senescence. This review aims to provide an integrated understanding of the regulation of PA metabolism and its effect(s) on cell homeostasis. PA metabolism is universal for plants and animals. Research has shown that increased levels of PA synthesizing enzymes are associated with cell proliferation, whereas activation of the PA catabolic pathway increases oxidative stress and leads to aging/senescence due to cellular damage. Intracellular PA levels are regulated at the transcriptional and translational levels of the PA metabolic genes. The cis-acting regulatory elements and transcription factors determine the tissue-, developmental stage-, and stress-specific expression of a gene. At the translational level, it is regulated by miRNAs targeting mRNAs for cleavage or translational suppression. The byproducts of PA metabolism, such as hypusine and acrolein, are important for cell survival or death. PAs and their metabolic enzymes play several other important roles in plant and animal physiology via their effects on chromatin condensation, histone acetylation, histone deacetylation, transmethylation, and protein-protein interactions. This review focuses on the role(s) of PAs as universal bioregulators in processes across kingdoms, with specific reference to regulation of cellular longevity and death.

Keywords:

• Biochemistry of polyamine metabolism
• polyamine-dependent transcription regulation
• polyamine-dependent translation regulation
• longevity
• aging
• cell death

Acknowledgments

We thank Richard Ashcroft (bioscience editor) for the professional language editing of the manuscript. ES is an Adam Mickiewicz University Foundation scholar in the 2022/2023 academic year.

Authors’ contributions

E.S.-N. conceived the topic of the article; E.S.-N. and E.S. were responsible for the layout of the manuscript, and were involved in the writing of the “Introduction” section; E.S. prepared the table and was involved in the writing of the “Polyamine metabolism and biochemistry—plants vs animals” section; U.K.T. was involved in the writing of the “Aspects of Regulation of Polyamine Metabolism” section; E.P.-L. was involved in the writing of the “Polyamine metabolism byproducts”; M.G. drew the figures and was involved in the writing of the “Polyamine role in regulation of gene expression” section; E.S.-N and M.A.-J. were involved in the writing of the “Polyamines and aging" section; E.S.-N. and E.S. were involved in the writing of the “Conclusions” section; O.P. IV and A.K.M. provided suggestions for revising the manuscript. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

The publication was co-financed within the National Science Center, Poland (project no. 2018/29/B/NZ9/00734 to E.S-N).