Nutritional influences on epigenetics and age-related disease

Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Proceedings of The Nutrition Society (Impact Factor: 5.27). 11/2011; 71(1):75-83. DOI: 10.1017/S0029665111003302
Source: PubMed


Nutritional epigenetics has emerged as a novel mechanism underlying gene-diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modulates gene expression without changes in the underlying bp sequence, ultimately determining phenotype from genotype. DNA methylation and post-translational histone modifications are classical levels of epigenetic regulation. Epigenetic phenomena are critical from embryonic development through the aging process, with aberrations in epigenetic patterns emerging as aetiological mechanisms in many age-related diseases such as cancer, CVD and neurodegenerative disorders. Nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications. Aging and age-related diseases are associated with profound changes in epigenetic patterns, though it is not yet known whether these changes are programmatic or stochastic in nature. Future work in this field seeks to characterise the epigenetic pattern of healthy aging to ultimately identify nutritional measures to achieve this pattern.

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    • "Nutriceuticals and multivitamins may extend longevity thanks to their chemo-protective effect against cancer through epigenetic mechanisms (Gerhauser, 2013), as well as against certain age-related diseases (Park et al., 2012), whilst being devoid of any toxic side effects. In fact, a significant decrease by up to 12% of cancers, other than prostate cancer, was observed in a double-blind prospective trial in general practitioners, after an average of 11.2 years use of a multivitamin supplement containing vitamins A and E (Gaziano et al., 2012) (NNT: 8.3). "
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    ABSTRACT: The long-term intake of a judiciously composed nutriceutical containing low-dose vitamins, antioxidants, minerals and particular herbal preparations seems justified for older persons who take medication, or who consume an unbalanced diet, or who are exposed to environmental toxins. Recent reports suggest these nutriceuticals may delay age-related diseases and the occurrence of cancer, and reduce mortality in apparently healthy ageing men. Food supplementation with a nutriceutical that was formulated particularly for ageing men should result in an increase of at least one quality-adjusted life year and may lower the financial and social burden of disease in elderly people.
    Andrologia 09/2015; DOI:10.1111/and.12489 · 1.63 Impact Factor
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    • "Similarly, deficiency of B vitamins, methionine, folic acid and/or choline can significantly alter DNA methylation by affecting levels of SAM and SAH [21] [22]. However, while these studies indicate the interaction between nutrients and the pathways regulating DNA methylation, it is still unclear how a specific gene is targeted by nutrients or alternatively, if these changes are stochastic in nature [21] [23]. "
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    ABSTRACT: Dietary interventions like gluten-free and casein-free diets have been reported to improve intestinal, autoimmune and neurological symptoms in patients with a variety of conditions; however, the underlying mechanism of benefit for such diets remains unclear. Epigenetic programming, including CpG methylation and histone modifications, occurring during early postnatal development can influence the risk of disease in later life, and such programming may be modulated by nutritional factors such as milk and wheat, especially during the transition from a solely milk-based diet to one that includes other forms of nutrition. The hydrolytic digestion of casein (a major milk protein) and gliadin (a wheat-derived protein) releases peptides with opioid activity, and in the present study, we demonstrate that these food-derived proline-rich opioid peptides modulate cysteine uptake in cultured human neuronal and gastrointestinal (GI) epithelial cells via activation of opioid receptors. Decreases in cysteine uptake were associated with changes in the intracellular antioxidant glutathione and the methyl donor S-adenosylmethionine. Bovine and human casein-derived opioid peptides increased genome-wide DNA methylation in the transcription start site region with a potency order similar to their inhibition of cysteine uptake. Altered expression of genes involved in redox and methylation homeostasis was also observed. These results illustrate the potential of milk- and wheat-derived peptides to exert antioxidant and epigenetic changes which may be particularly important during the postnatal transition from placental to GI nutrition. Differences between peptides derived from human and bovine milk may contribute to developmental differences between breastfed and formula-fed infants. Restricted antioxidant capacity, caused by wheat- and milk-derived opioid peptides, may predispose susceptible individuals to inflammation and systemic oxidation, partly explaining the benefits of gluten-free or casein-free diets.
    The Journal of Nutritional Biochemistry 10/2014; 25(10). DOI:10.1016/j.jnutbio.2014.05.004 · 3.79 Impact Factor
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    • "On the contrary, food for mothers and infants containing enough compounds for an adequate epigenomic programing are assumed to be of importance for health later in life (18, 27, 77–81). However, as underlined by Park et al. (77), in this field, ‘there is much to be done that has great potential to yield findings with significant public health implication’. "
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    ABSTRACT: It is now generally accepted that the 'central genome dogma' (i.e. a causal chain going from DNA to RNA to proteins and downstream to biological functions) should be replaced by the 'fluid genome dogma', that is, complex feed-forward and feed-back cycles that interconnect organism and environment by epigenomic programing - and reprograming - throughout life and at all levels, sometimes also down the generations. The epigenomic programing is the net sum of interactions derived from own metabolism and microbiota as well as external factors such as diet, pharmaceuticals, environmental compounds, and so on. It is a growing body of results indicating that many chronic metabolic and degenerative disorders and diseases - often called 'civilization diseases' - are initiated and/or influenced upon by non-optimal epigenomic programing, often taking place early in life. In this context, the first 1,000 days of life - from conception into early infancy - is often called the most important period of life. The following sections present some major mechanisms for epigenomic programing as well as some factors assumed to be of importance. The need for more information about own genome and metagenome, as well as a substantial lack of adequate information regarding dietary and environmental databases are also commented upon. However, the mere fact that we can influence epigenomic health programing opens up the way for prophylactic and therapeutic interventions. The authors underline the importance of creating a 'Human Gut Microbiota and Epigenomic Platform' in order to facilitate interdisciplinary collaborations among scientists and clinicians engaged in host microbial ecology, nutrition, metagenomics, epigenomics and metabolomics as well as in disease epidemiology, prevention and treatment.
    Microbial Ecology in Health and Disease 05/2014; 25. DOI:10.3402/mehd.v25.24145
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