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From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition?

Szarc vel Szic K, Declerck K, Vidaković M, Vanden Berghe W - Clin Epigenetics (2015)

Bottom Line: Chronic low-grade systemic inflammation during physiological aging and immunosenescence are intertwined in the pathogenesis of premature aging also defined as 'inflammaging.' The latter has been associated with frailty, morbidity, and mortality in elderly subjects.Remarkably, humans present a broad range of responses to similar dietary challenges due to both genetic and epigenetic modulations of the expression of target proteins and key genes involved in the metabolism and distribution of the dietary constituents.Here, we will summarize the epigenetic actions of dietary components, including phytochemicals, and macro- and micronutrients as well as metabolites, that can attenuate inflammaging.

View Article: PubMed Central - PubMed

Affiliation: Lab Protein Science, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium.

ABSTRACT
The progressively older population in developed countries is reflected in an increase in the number of people suffering from age-related chronic inflammatory diseases such as metabolic syndrome, diabetes, heart and lung diseases, cancer, osteoporosis, arthritis, and dementia. The heterogeneity in biological aging, chronological age, and aging-associated disorders in humans have been ascribed to different genetic and environmental factors (i.e., diet, pollution, stress) that are closely linked to socioeconomic factors. The common denominator of these factors is the inflammatory response. Chronic low-grade systemic inflammation during physiological aging and immunosenescence are intertwined in the pathogenesis of premature aging also defined as 'inflammaging.' The latter has been associated with frailty, morbidity, and mortality in elderly subjects. However, it is unknown to what extent inflammaging or longevity is controlled by epigenetic events in early life. Today, human diet is believed to have a major influence on both the development and prevention of age-related diseases. Most plant-derived dietary phytochemicals and macro- and micronutrients modulate oxidative stress and inflammatory signaling and regulate metabolic pathways and bioenergetics that can be translated into stable epigenetic patterns of gene expression. Therefore, diet interventions designed for healthy aging have become a hot topic in nutritional epigenomic research. Increasing evidence has revealed that complex interactions between food components and histone modifications, DNA methylation, non-coding RNA expression, and chromatin remodeling factors influence the inflammaging phenotype and as such may protect or predispose an individual to many age-related diseases. Remarkably, humans present a broad range of responses to similar dietary challenges due to both genetic and epigenetic modulations of the expression of target proteins and key genes involved in the metabolism and distribution of the dietary constituents. Here, we will summarize the epigenetic actions of dietary components, including phytochemicals, and macro- and micronutrients as well as metabolites, that can attenuate inflammaging. We will discuss the challenges facing personalized nutrition to translate highly variable interindividual epigenetic diet responses to potential individual health benefits/risks related to aging disease.

No MeSH data available.


Related in: MedlinePlus

Metabolic pathways generate essential metabolites for chromatin- and DNA-modifying enzymes. NAD, acetyl-coenzyme A (Acetyl-coA), and S-adenosylmethionine (SAM) are elemental for epigenetic control of transcription including methylation of DNA and posttranslational modifications of histones and non-histone chromatin factors (not shown). NAD contributes to transcriptional control mainly via the activity of the protein deacetylase sirtuin, which uses NAD as one of the substrates. Sirtuins are also important for maintaining the activity of the acetyl-coA acetyltransferases. Acetyl-coA is synthesized by acetyl-coA-synthetase (ACS) and ATP-citrate lyase that use acetate and citrate as the precursors, respectively. Citrate is an intermediate/product of the TCA cycle. SAM is the methyl donor for DNA, RNA, histones, and non-histone protein methylation. S-adenosylhomocysteine (SAH) generated in each round of methylation reaction is a potent inhibitor of methyltransferases and has to be cleared by SAH hydrolase (SAHH). NAD is an essential coenzyme for SAHH. Synthesis of methionine from homocystein is achieved through extracting the methyl group from betaine, derived from choline, or 5-methyl-THF, a derivative of folic acid. Metabolism of phospholipids and folic acid may thus indirectly contribute to epigenetic regulation. Likewise, the abundance of NAD and citrate is linked to the cellular energy flux, e.g., the TCA cycle. Changes in the expression of certain genes may therefore be influenced significantly. Abbreviations used: Acetyl-coA, acetyl-coenzyme A; ACS, acetyl-coA-synthetase; AC-ACS acetylated-ACS; Ado, adenosine; HAT, histone acetyltransferase; Hcy homocysteine; MTases, methyltransferases; NAD, Nicotinamide adenine dinucleotide; ROS, reactive oxygen species, RNS, reactive nitrogen species, SAH, S-adenosyl homocysteine; TCA, tricarboxylic cycle; THF, tetrahydrofolate.
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Fig1: Metabolic pathways generate essential metabolites for chromatin- and DNA-modifying enzymes. NAD, acetyl-coenzyme A (Acetyl-coA), and S-adenosylmethionine (SAM) are elemental for epigenetic control of transcription including methylation of DNA and posttranslational modifications of histones and non-histone chromatin factors (not shown). NAD contributes to transcriptional control mainly via the activity of the protein deacetylase sirtuin, which uses NAD as one of the substrates. Sirtuins are also important for maintaining the activity of the acetyl-coA acetyltransferases. Acetyl-coA is synthesized by acetyl-coA-synthetase (ACS) and ATP-citrate lyase that use acetate and citrate as the precursors, respectively. Citrate is an intermediate/product of the TCA cycle. SAM is the methyl donor for DNA, RNA, histones, and non-histone protein methylation. S-adenosylhomocysteine (SAH) generated in each round of methylation reaction is a potent inhibitor of methyltransferases and has to be cleared by SAH hydrolase (SAHH). NAD is an essential coenzyme for SAHH. Synthesis of methionine from homocystein is achieved through extracting the methyl group from betaine, derived from choline, or 5-methyl-THF, a derivative of folic acid. Metabolism of phospholipids and folic acid may thus indirectly contribute to epigenetic regulation. Likewise, the abundance of NAD and citrate is linked to the cellular energy flux, e.g., the TCA cycle. Changes in the expression of certain genes may therefore be influenced significantly. Abbreviations used: Acetyl-coA, acetyl-coenzyme A; ACS, acetyl-coA-synthetase; AC-ACS acetylated-ACS; Ado, adenosine; HAT, histone acetyltransferase; Hcy homocysteine; MTases, methyltransferases; NAD, Nicotinamide adenine dinucleotide; ROS, reactive oxygen species, RNS, reactive nitrogen species, SAH, S-adenosyl homocysteine; TCA, tricarboxylic cycle; THF, tetrahydrofolate.

Mentions: Tissues and cells of aging organisms also show age-associated changes in histone chromatin marks such as increased histone H4 lysine(K)16 acetylation, H4K20 trimethylation, or H3K4 trimethylation, as well as decreased H3K9 methylation [73-75]. Age-associated epigenomic changes could be driven by changes in expression of chromatin-modifying or -demodifying enzymes [75-77]. Of particular interest, deletion of components of histone methylation complexes (for H3K4 and for H3K27) extends longevity in nematodes and flies, respectively, and may involve the insulin/IGF-1 signaling pathway [78-81]. It is not yet clear whether aging is a cause or consequence following purely epigenetic changes or alterations affecting metabolic or signaling pathways outside of the nucleus. Importantly, since the activities of histone-modifying enzymes also depend on intracellular levels of essential metabolites (acetyl-coA, Fe, ketoglutarate, NAD+, S-adenosylmethionine), epigenetic changes are tightly linked to global cellular metabolism and energy levels [82-88] (Figure 1). Finally, ROS (such as •O2, •OH, H2O2, NO, and 1O2) as well as reactive nitrogen intermediates such and NO and reactive nitrogen species (RNS), produced by neutrophils, macrophages, endothelial, and other cells, can indirectly modulate the activity of the epigenetic machinery. For example, ROS were demonstrated to modulate the activity of the Rph1 demethylase specifically at subtelomeres to remodel chromatin and extend lifespan [89].Figure 1


From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition?

Szarc vel Szic K, Declerck K, Vidaković M, Vanden Berghe W - Clin Epigenetics (2015)

Metabolic pathways generate essential metabolites for chromatin- and DNA-modifying enzymes. NAD, acetyl-coenzyme A (Acetyl-coA), and S-adenosylmethionine (SAM) are elemental for epigenetic control of transcription including methylation of DNA and posttranslational modifications of histones and non-histone chromatin factors (not shown). NAD contributes to transcriptional control mainly via the activity of the protein deacetylase sirtuin, which uses NAD as one of the substrates. Sirtuins are also important for maintaining the activity of the acetyl-coA acetyltransferases. Acetyl-coA is synthesized by acetyl-coA-synthetase (ACS) and ATP-citrate lyase that use acetate and citrate as the precursors, respectively. Citrate is an intermediate/product of the TCA cycle. SAM is the methyl donor for DNA, RNA, histones, and non-histone protein methylation. S-adenosylhomocysteine (SAH) generated in each round of methylation reaction is a potent inhibitor of methyltransferases and has to be cleared by SAH hydrolase (SAHH). NAD is an essential coenzyme for SAHH. Synthesis of methionine from homocystein is achieved through extracting the methyl group from betaine, derived from choline, or 5-methyl-THF, a derivative of folic acid. Metabolism of phospholipids and folic acid may thus indirectly contribute to epigenetic regulation. Likewise, the abundance of NAD and citrate is linked to the cellular energy flux, e.g., the TCA cycle. Changes in the expression of certain genes may therefore be influenced significantly. Abbreviations used: Acetyl-coA, acetyl-coenzyme A; ACS, acetyl-coA-synthetase; AC-ACS acetylated-ACS; Ado, adenosine; HAT, histone acetyltransferase; Hcy homocysteine; MTases, methyltransferases; NAD, Nicotinamide adenine dinucleotide; ROS, reactive oxygen species, RNS, reactive nitrogen species, SAH, S-adenosyl homocysteine; TCA, tricarboxylic cycle; THF, tetrahydrofolate.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4389409&req=5

Fig1: Metabolic pathways generate essential metabolites for chromatin- and DNA-modifying enzymes. NAD, acetyl-coenzyme A (Acetyl-coA), and S-adenosylmethionine (SAM) are elemental for epigenetic control of transcription including methylation of DNA and posttranslational modifications of histones and non-histone chromatin factors (not shown). NAD contributes to transcriptional control mainly via the activity of the protein deacetylase sirtuin, which uses NAD as one of the substrates. Sirtuins are also important for maintaining the activity of the acetyl-coA acetyltransferases. Acetyl-coA is synthesized by acetyl-coA-synthetase (ACS) and ATP-citrate lyase that use acetate and citrate as the precursors, respectively. Citrate is an intermediate/product of the TCA cycle. SAM is the methyl donor for DNA, RNA, histones, and non-histone protein methylation. S-adenosylhomocysteine (SAH) generated in each round of methylation reaction is a potent inhibitor of methyltransferases and has to be cleared by SAH hydrolase (SAHH). NAD is an essential coenzyme for SAHH. Synthesis of methionine from homocystein is achieved through extracting the methyl group from betaine, derived from choline, or 5-methyl-THF, a derivative of folic acid. Metabolism of phospholipids and folic acid may thus indirectly contribute to epigenetic regulation. Likewise, the abundance of NAD and citrate is linked to the cellular energy flux, e.g., the TCA cycle. Changes in the expression of certain genes may therefore be influenced significantly. Abbreviations used: Acetyl-coA, acetyl-coenzyme A; ACS, acetyl-coA-synthetase; AC-ACS acetylated-ACS; Ado, adenosine; HAT, histone acetyltransferase; Hcy homocysteine; MTases, methyltransferases; NAD, Nicotinamide adenine dinucleotide; ROS, reactive oxygen species, RNS, reactive nitrogen species, SAH, S-adenosyl homocysteine; TCA, tricarboxylic cycle; THF, tetrahydrofolate.
Mentions: Tissues and cells of aging organisms also show age-associated changes in histone chromatin marks such as increased histone H4 lysine(K)16 acetylation, H4K20 trimethylation, or H3K4 trimethylation, as well as decreased H3K9 methylation [73-75]. Age-associated epigenomic changes could be driven by changes in expression of chromatin-modifying or -demodifying enzymes [75-77]. Of particular interest, deletion of components of histone methylation complexes (for H3K4 and for H3K27) extends longevity in nematodes and flies, respectively, and may involve the insulin/IGF-1 signaling pathway [78-81]. It is not yet clear whether aging is a cause or consequence following purely epigenetic changes or alterations affecting metabolic or signaling pathways outside of the nucleus. Importantly, since the activities of histone-modifying enzymes also depend on intracellular levels of essential metabolites (acetyl-coA, Fe, ketoglutarate, NAD+, S-adenosylmethionine), epigenetic changes are tightly linked to global cellular metabolism and energy levels [82-88] (Figure 1). Finally, ROS (such as •O2, •OH, H2O2, NO, and 1O2) as well as reactive nitrogen intermediates such and NO and reactive nitrogen species (RNS), produced by neutrophils, macrophages, endothelial, and other cells, can indirectly modulate the activity of the epigenetic machinery. For example, ROS were demonstrated to modulate the activity of the Rph1 demethylase specifically at subtelomeres to remodel chromatin and extend lifespan [89].Figure 1

Bottom Line: Chronic low-grade systemic inflammation during physiological aging and immunosenescence are intertwined in the pathogenesis of premature aging also defined as 'inflammaging.' The latter has been associated with frailty, morbidity, and mortality in elderly subjects.Remarkably, humans present a broad range of responses to similar dietary challenges due to both genetic and epigenetic modulations of the expression of target proteins and key genes involved in the metabolism and distribution of the dietary constituents.Here, we will summarize the epigenetic actions of dietary components, including phytochemicals, and macro- and micronutrients as well as metabolites, that can attenuate inflammaging.

View Article: PubMed Central - PubMed

Affiliation: Lab Protein Science, Proteomics and Epigenetic Signaling, Department of Biomedical Sciences, University Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium.

ABSTRACT
The progressively older population in developed countries is reflected in an increase in the number of people suffering from age-related chronic inflammatory diseases such as metabolic syndrome, diabetes, heart and lung diseases, cancer, osteoporosis, arthritis, and dementia. The heterogeneity in biological aging, chronological age, and aging-associated disorders in humans have been ascribed to different genetic and environmental factors (i.e., diet, pollution, stress) that are closely linked to socioeconomic factors. The common denominator of these factors is the inflammatory response. Chronic low-grade systemic inflammation during physiological aging and immunosenescence are intertwined in the pathogenesis of premature aging also defined as 'inflammaging.' The latter has been associated with frailty, morbidity, and mortality in elderly subjects. However, it is unknown to what extent inflammaging or longevity is controlled by epigenetic events in early life. Today, human diet is believed to have a major influence on both the development and prevention of age-related diseases. Most plant-derived dietary phytochemicals and macro- and micronutrients modulate oxidative stress and inflammatory signaling and regulate metabolic pathways and bioenergetics that can be translated into stable epigenetic patterns of gene expression. Therefore, diet interventions designed for healthy aging have become a hot topic in nutritional epigenomic research. Increasing evidence has revealed that complex interactions between food components and histone modifications, DNA methylation, non-coding RNA expression, and chromatin remodeling factors influence the inflammaging phenotype and as such may protect or predispose an individual to many age-related diseases. Remarkably, humans present a broad range of responses to similar dietary challenges due to both genetic and epigenetic modulations of the expression of target proteins and key genes involved in the metabolism and distribution of the dietary constituents. Here, we will summarize the epigenetic actions of dietary components, including phytochemicals, and macro- and micronutrients as well as metabolites, that can attenuate inflammaging. We will discuss the challenges facing personalized nutrition to translate highly variable interindividual epigenetic diet responses to potential individual health benefits/risks related to aging disease.

No MeSH data available.


Related in: MedlinePlus