Epigenetic Diet and Longer Lifespan
Epigenetic mechanisms, including DNA methylation, histone modification, and RNA interference, have been shown to play crucial roles in regulating the expression of genes that are involved in age-related diseases and longevity [1]. These mechanisms are mediated by modifying histone enzymes and noncoding RNAs. However, several environmental and dietary factors can lead to their imbalance, leading to abnormalities that affect health and longevity.
What Is the Epigenome?
The epigenome is a set of chemical modifications of the DNA and DNA-related proteins that are involved in regulating gene expression in physiological and pathological conditions, including age-related diseases.
Environmental and dietary factors, such as nutritional factors and chemicals have been directly implicated in altering the epigenome through mechanisms involving DNA methylation and histone modification, leading to the development of abnormalities that affect health and longevity [2].
How do Bioactive Compounds Affect the Epigenome?
Interestingly, several studies have demonstrated that several bioactive compounds, such as the ones found in fruit, vegetables, and plants, can positively affect the epigenome, contributing to improvements in longevity.
These natural compounds can influence a relaxed or closed chromatin form that determines the DNA accessibility of transcription factors that are involved in transcriptional and functional processes involved in aging and longevity (Lifespan).
What Are the Bioactive Compounds That Affect the Epigenome?
Resveratrol, sulforaphane, and curcumin can act on relaxed and closed forms of the chromatin, while others, such as Genistein can promote a relaxed form of chromatin, and Epigallocatechin-3-gallate can act oppositely by promoting a closed-form of chromatin [3] [4].
How Does Resveratrol Prolong Longevity?
Resveratrol is a polyphenol found in red wine that has antiaging and anti-diabetic properties and is used as a nutritional supplement. Resveratrol has been shown to increase the levels of the NAD-dependent deacetylase sirtuin-1 (SIRT-1), a protein that is involved in the cellular response to inflammatory, metabolic, and oxidative stressors.
Resveratrol metabolic activity appears to be mediated through the inhibition of the cAMP-degrading phosphodiesterase that results in increased levels of SIRT-1 and NAD+ leading to histones deacetylation and chromatin relaxation [5].
How Does Sulforaphane Prolong Longevity?
Sulforaphane (SFN) is an isothiocyanate that is present in cruciferous vegetables such as cauliflower, cabbage, kale, garden cress, bok choy, broccoli, and Brussels sprouts. In addition to its epigenetic effect through the inhibition of HDAC and DNA methyltransferases which relaxes the chromatin [6], Sulforaphane also inhibits inflammation by inhibiting NFkB and promotes antioxidation via the induction of NrF2, a master regulator of detoxification, anti-inflammation, and antioxidation processes within the cells.
How Does Curcumin Prolong Longevity?
Curcumin is a bioactive polyphenolic extract of turmeric that is used as a spice, food additive, and herbal medicine. Although curcumin increases longevity through the induction of the activity of the antioxidant superoxide dismutase (SOD), but also through other pathways, it also significantly inhibits histone acetylation which promotes chromatin relaxation promoting DNA accessibility to longevity and anti-aging transcription factors [7].
How Does Genistein Prolong Longevity?
Genistein is an isoflavone that is found in plants such as soybeans and fava beans and is used as a dietary supplement. Genistein has been shown to have anti-cancer and antiaging properties. It functions by increasing histone acetylation through the induction of histone acetyltransferases which relaxes the chromatin allowing access for transcriptional regulatory factors [8].
How Does Epigallocatechin-3-gallate Prolong Longevity?
Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol component of green tea that has been shown to have benefits for health and longevity. EGCG promotes chromatin relaxation by affecting the expression and activity of epigenome modulators such as HDAC5 and 7, p300, CREBP, LSD1, or KMT2A [9].
How Does Garlic Prolong Longevity?
Garlic through its organosulfur compounds such as diallyl sulfide, diallyl disulfide, and diallyl trisulfide, have been shown to alter the activity of histone deacetylases (HDACs) which derepresses epigenetically silenced genes that may be involved in anti-aging and longevity [11].
How Do Environmental Exposures Affect the Epigenome?
Many studies investigated the changes in the epigenome following exposures to chemicals and air pollution. For instance, air pollution through particulate matter (PM) exposure results in gene-specific methylation in workers of steel plants. Benzene exposure was also shown to alter DNA methylation resulting in aberrations similar to the ones observed in cancer cells.
Exposure to the environmental contaminants, Trichloroethylene (TCE), dichloroacetic acid (DCA), and trichloroacetic acid (TCA) was reported to prevent DNA hypomethylation. Other types of exposure such to the metals nickel, cadmium, lead, and arsenic are also involved in Oxidative DNA damage which can interfere with the ability of methyltransferases to interact with DNA [10].
Interestingly some environmental pollutants such as alloxan, cyclophosphamide, orthoaminoasotoluol, benzopyrene, diethylstilbestrol (DES), and vinclozolin have been reported to induce transgenerational phenotypic effects that cause abnormalities in the offspring for at least three generations [10].
Conclusion
Considering that these bioactive compounds play different roles in regulating the longevity-related epigenome, perhaps, determining the right dietary amounts may further improve their longevity benefits. On the other hand, some chemicals and air pollutants would have reverse effects on health and longevity.
References
[1]Booth, Lauren N., and Anne Brunet. “The aging epigenome.” Molecular cell 62.5 (2016): 728-744.
