Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation

Abstract

Polyamines, spermidine and spermine, are synthesized in every living cell and are therefore contained in foods, especially in those that are thought to contribute to health and longevity. They have many physiological activities similar to those of antioxidant and anti-inflammatory substances such as polyphenols. These include antioxidant and anti-inflammatory properties, cell and gene protection, and autophagy activation. We have first reported that increased polyamine intake (spermidine much more so than spermine) over a long period increased blood spermine levels and inhibited aging-associated pathologies and pro-inflammatory status in humans and mice and extended life span of mice. However, it is unlikely that the life-extending effect of polyamines is exerted by the same bioactivity as polyphenols because most studies using polyphenols and antioxidants have failed to demonstrate their life-extending effects. Recent investigations revealed that aging-associated pathologies and lifespan are closely associated with DNA methylation, a regulatory mechanism of gene expression. There is a close relationship between polyamine metabolism and DNA methylation. We have shown that the changes in polyamine metabolism affect the concentrations of substances and enzyme activities involved in DNA methylation. I consider that the increased capability of regulation of DNA methylation by spermine is a key of healthy long life of humans.

The Role of Polyamines in the Mechanisms of Cognitive Impairment

“…In addition, antizymes are able to inhibit the absorption of polyamines or stimulate their secretion. The existence of 3 forms of AZI antizymes has been shown: AZI 1, AZI 2, and AZI 3 [ 21 ]. A more complex regulation of ODC activity is provided by antizyme inhibitor (AZIN) proteins, which are able to interact with AZI with a higher affinity than with ODC.…”

“…A more complex regulation of ODC activity is provided by antizyme inhibitor (AZIN) proteins, which are able to interact with AZI with a higher affinity than with ODC. Currently, two forms have been identified: AZIN 1 and AZIN 2 [ 21 ].…”

“…Transport of polyamines into the cell is carried out by OCT transporters (organic cation transporter) [ 21 ].…”

“…The administration of aldehyde dehydrogenase, an enzyme that eliminates acrolein, into a neuronal culture containing toxic doses of spermine prevented cell death [ 23 ]. Using a model of ischemia caused by glucose-oxygen deprivation in neuroblastoma culture, M. Nakamura et al found that it is Ca 2+ that induces the toxicity of polyamines, while in the neuron there is a decrease in the content of polyamines and an increase in the formation of their decay products (PCAcrolein) [ 21 ]. One of the main pathways for Ca 2+ entry into neurons is AMPA and NMDA receptor channels.…”

“…One of the main pathways for Ca 2+ entry into neurons is AMPA and NMDA receptor channels. Animal experiments have shown that the administration of N1, N4, N8 tribenzylspermidine, an NMDA receptor channel blocker, leads to a decrease in the content of Ca 2+ and PCAcrolein in neurons, which is associated with a decrease in the size of the brain infarction focus [ 21 ]. It is established that glial polyamines are able to protect neurons from death by regulating these neuronal receptor channels [ 31 ].…”