Abstract
Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.
Highlights
Aging is associated with declines in physiological function, altered immune function, increased proinflammatory status, and increased susceptibility to pathologies such as cardiovascular disease, cancer, sarcopenia, and metabolic and neurodegenerative diseases
We have shown that aliphatic polyamines contained in foods reduce the proinflammatory status and regulate enzymatic activities involved in gene methylation and the methylation status of the entire genome [19,45]
These facts suggest that diet has great impact on DNA methylation, and this has been proven in experimental studies
Summary
Aging is associated with declines in physiological function, altered immune function, increased proinflammatory status, and increased susceptibility to pathologies such as cardiovascular disease, cancer, sarcopenia, and metabolic and neurodegenerative diseases. A mediterranean diet and increased vegetable intake are associated with a decreased incidence of lifestyle-related diseases, such as CVDs [11,12,13] and breast and colon cancer [14,15,16,17] These findings indicate that ingredients contained in these foods may play an important role in the inhibition of aging-associated pathologies. Low-level elevation of proinflammatory cytokines and chemokines, and the resulting increases in inflammatory biomarkers, are associated with age-related declines in function as well as increased risks of morbidity and mortality [21] Based on this background, substances contained in foods that inhibit or counteract the aging-associated proinflammatory status and decrease resulting increases in oxidative stress (i.e., chemicals that inhibit the transfer of electrons from a substance to an oxidizing agent) have attracted scientists’ interest. The current review will discuss the relation between DNA methylation and various nutrients, as well as the mechanism by which dietary polyamines affect DNA methylation and inhibit aging-associated pathologies
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