Polyamines in aging and disease

Abstract

Polyamines are polycations that interact with negatively charged molecules such as DNA, RNA and proteins. They play multiple roles in cell growth, survival and proliferation. Changes in polyamine levels have been associated with aging and diseases. Their levels decline continuously with age and polyamine (spermidine or high-polyamine diet) supplementation increases life span in model organisms. Polyamines have also been involved in stress resistance. On the other hand, polyamines are increased in cancer cells and are a target for potential chemotherapeutic agents. In this review, we bring together these various results and draw a picture of the state of our knowledge on the roles of polyamines in aging, stress and diseases.

Figure 1. Putrescine, spermidine and spermine chemical structure

Figure 2. Polyamine metabolism. Green: biosynthesis; blue: catabolism; red: inhibitory protein; black: eIF5A synthesis from spermidine

Figure 3. Summary of the cellular mechanisms of action of polyamines

Upon entering the cell, polyamines exhibit various functions in the cytoplasm, nucleus and mitochondria. Polyamines are involved in the regulation of cell death and cell proliferation as well as in protein synthesis at the level of both gene expression and translation. Recent evidence also assigned polyamines functions in cell reprogramming and autophagy regulation. Thus, polyamines are involved in a broad array of processes and cellular responses that suggest a complex and important role in the control of cellular life and death. PT: permeability transition; Δψm: mitochondrial membrane potential.