Can age be a modifiable risk factor? the impact of dietary patterns on the molecular mechanisms that underlie cardiovascular aging

Abstract

Aging is the number one risk factor for the development of cardiovascular disease (CVD). Therefore, an evaluation of therapies for the prevention of CVD should focus on factors that slow down aging, particularly cardiovascular aging. There are various proposed mechanisms that advance cardiovascular age; in this review, we focus on chronic inflammation, oxidative stress and epigenetics as the primary drivers of aging. Furthermore, we will evaluate several dietary patterns on their impact on these aging mechanisms. The traditional "heart-healthy" dietary patterns such as the Mediterranean diet, plant-based diet and intermittent fasting will be evaluated for their performance to slow down the aforementioned aging mechanisms. The aim of this review will be to guide practitioners and patients on the dietary components that can slow down the effects of aging to prevent CVD.

Keywords

Cardiovascular aging / dietary patterns / chronic inflammation / epigenetics / oxidative stress

References

[1] Gilbert SF. Developmental biology. Sunderland: Sinauer Associates, Inc.; 2010.

[2] North BJ.The intersection between aging and cardiovascular disease.Circ Res2012;110:1097-108 PMCID:PMC3366686

[3] Goff Jr DC,Bennett G.2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.Circulation2014;129:S49-S73

[4] Heidenreich PA,Khavjou OA.Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.Circulation2011;123:933-44

[5] Fleg JL,Frishman WH.Cardiovascular drug therapy in the elderly: benefits and challenges.Nat Rev Cardiol2011;8:13-28

[6] Afshin A,Fay KA.Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.Lancet2019;393:1958-72 PMCID:PMC6899507

[7] Kim H,Garcia-Larsen V,Coresh J.Plant-based diets are associated with a lower risk of incident cardiovascular disease, cardiovascular disease mortality, and all-cause mortality in a general population of middle-aged adults.J Am Heart Assoc2019;8:e012865 PMCID:PMC6759882

[8] Yokoyama Y,Barnard ND.Vegetarian diets and blood pressure: a meta-analysis.JAMA Int Med2014;174:577-87

[9] Razavi AC,He J.Consumption of animal and plant foods and risk of left ventricular diastolic dysfunction: the Bogalusa Heart Study.ESC Heart Fail2020;7:2700-10 PMCID:PMC7524109

[10] Pietri P.Cardiovascular aging and longevity: JACC state-of-the-art review.J Am Coll Cardiol2021;77:189-204

[11] Stern S,Gottlieb S.Aging and diseases of the heart.Circulation2003;108:e99-e101

[12] Estruch R,Salas-Salvadó J.Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts.New Engl J Med2018;379:1388

[13] Appel LJ,Daniels SR,Elmer PJ.Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association.Hypertension2006;47:296-308

[14] Dybvik JS,Aune D.Vegetarian and vegan diets and the risk of cardiovascular disease, ischemic heart disease and stroke: a systematic review and meta-analysis of prospective cohort studies.Eur J Nutr2022:1-19 PMCID:PMC9899747

[15] Franceschi C,Garagnani P,Monti D.Immunobiography and the heterogeneity of immune responses in the elderly: a focus on inflammaging and trained immunity.Front Immunol2017;8:982 PMCID:PMC5559470

[16] Ferrucci L.Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty.Nat Rev Cardiol2018;15:505-22 PMCID:PMC6146930

[17] Petrie JR,Touyz RM.Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms.Can J Cardiol2018;34:575-84 PMCID:PMC5953551

[18] Bobryshev YV,Chistiakov DA,Orekhov AN.Macrophages and their role in atherosclerosis: pathophysiology and transcriptome analysis.Biomed Res Int2016;2016:9582430 PMCID:PMC4967433

[19] Malinowski B,Węsierska A.Intermittent fasting in cardiovascular disorders-an overview.Nutrients2019;11:673 PMCID:PMC6471315

[20] Gude NA,Firouzi F.Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence.Nat Rev Cardiol2018;15:523-42

[21] Gorenne I,Scott S.Vascular smooth muscle cell senescence in atherosclerosis.Cardiovasc Res2006;72:9-17

[22] Minamino T,Yoshida T,Yoshida H.Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction.Circulation2002;105:1541-4

[23] Morgan RG,Lesniewski LA.Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries.Am J Physiol Heart Circ Physiol2013;305:H251-8 PMCID:PMC3726958

[24] Sun Y,Liu T,Pan X.The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities.Cell Biosci2022;12:74 PMCID:PMC9153125

[25] Childs BG,Wijshake T,Campisi J.Senescent intimal foam cells are deleterious at all stages of atherosclerosis.Science2016;354:472-7 PMCID:PMC5112585

[26] Stojanović SD,Kunz M.Inflammatory drivers of cardiovascular disease: molecular characterization of senescent coronary vascular smooth muscle cells.Front Physiol2020;11:520 PMCID:PMC7261939

[27] Demaria M,Youssef SA.An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.Dev Cell2014;31:722-33 PMCID:PMC4349629

[28] Liberale L,Tardif JC,Camici GG.Inflamm-ageing: the role of inflammation in age-dependent cardiovascular disease.Eur Heart J2020;41:2974-82 PMCID:PMC7453832

[29] Wang M,Monticone RE.Matrix metalloproteinases promote arterial remodeling in aging, hypertension, and atherosclerosis.Hypertension2015;65:698-703 PMCID:PMC4359070

[30] Jones NL,Willingham MC.The pathogenesis of foam cell formation: modified LDL stimulates uptake of co-incubated LDL via macropinocytosis.Arterioscler Thromb Vasc Biol2000;20:773-81

[31] Singh SK,Voleti B.The connection between C-reactive protein and atherosclerosis.Ann Med2008;40:110-20 PMCID:PMC3364506

[32] Anthony SR,Gozdiff A,Phillip Owens A.Mechanisms linking adipose tissue inflammation to cardiac hypertrophy and fibrosis.Clin Sci2019;133:2329-44 PMCID:PMC7191542

[33] Park YM,Vieira-Potter VJ.Adipose tissue inflammation and metabolic dysfunction: role of exercise.Mo Med2014;111:65-72. PMCID:PMC6179510

[34] Wilcox G.Insulin and insulin resistance.Clin Biochem Rev2005;26:19-39. PMCID:PMC1204764

[35] Khafagy R.Obesity and cardiovascular disease: the emerging role of inflammation.Front Cardiovasc Med2021;8:768119 PMCID:PMC8573144

[36] Ormazabal V,Elfeky O,Salomon C.Association between insulin resistance and the development of cardiovascular disease.Cardiovasc Diabetol2018;17:122 PMCID:PMC6119242

[37] Kaur N,Raja R,Liu W.Mechanisms and therapeutic prospects of diabetic cardiomyopathy through the inflammatory response.Front Physiol2021;12:694864 PMCID:PMC8257042

[38] Wu PY,Tsai WC.The mediterranean dietary pattern and inflammation in older adults: a systematic review and meta-analysis.Adv Nutr2021;12:363-73 PMCID:PMC8009747

[39] Tsigalou C,Paraschaki A,Voidarou C.Mediterranean diet as a tool to combat inflammation and chronic diseases. an overview.Biomedicines2020;8:201 PMCID:PMC7400632

[40] Mena MP,Vazquez-Agell M.Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet.Am J Clin Nutr2009;89:248-56

[41] Bonaccio M,De Curtis A.Adherence to the mediterranean diet is associated with lower platelet and leukocyte counts: results from the moli-sani study.Blood2014;123:3037-44

[42] Merra G,Marrone G.Influence of mediterranean diet on human gut microbiota.Nutrients2020;13:7 PMCID:PMC7822000

[43] Meslier V,Roager HM.Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake.Gut2020;69:1258-68 PMCID:PMC7306983

[44] Kimble R,Ashor A.Effects of a mediterranean diet on the gut microbiota and microbial metabolites: A systematic review of randomized controlled trials and observational studies.Crit Rev Food Sci Nutr2022;2022:1-22

[45] Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study.Circulation1999;99:779-85

[46] Shikany JM,Soroka O.Mediterranean diet score, dietary patterns, and risk of sudden cardiac death in the regards study.J Am Heart Assoc2021;10:e019158 PMCID:PMC8403280

[47] Esposito K,Di Palo C.Adherence to a mediterranean diet and glycaemic control in type 2 diabetes mellitus.Diabet Med2009;26:900-7

[48] Esposito K,Ciotola M.Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial.JAMA2004;292:1440-6

[49] Estruch R,Corella D.Effects of a mediterranean-style diet on cardiovascular risk factors: a randomized trial.Ann Intern Med2006;145:1-11

[50] Martín-Peláez S,Castaner O.Mediterranean diet effects on type 2 diabetes prevention, disease progression, and related mechanisms: a review.Nutrients2020;12:2236 PMCID:PMC7468821

[51] Sleiman D,Azar ST.Effect of mediterranean diet in diabetes control and cardiovascular risk modification: a systematic review.Front Public Health2015;3:69 PMCID:PMC4411995

[52] Menzel J,Longree A.Associations of a vegan diet with inflammatory biomarkers.Sci Rep2020;10:1933 PMCID:PMC7005174

[53] Haghighatdoost F,Totosy de Zepetnek JO.Association of vegetarian diet with inflammatory biomarkers: a systematic review and meta-analysis of observational studies.Public Health Nutr2017;20:2713-21

[54] Menzel J,Biemann R,Abraham K.Systematic review and meta-analysis of the associations of vegan and vegetarian diets with inflammatory biomarkers.Sci Rep2020;10:21736 PMCID:PMC7730154

[55] Szabo Z,Marosvolgyi T.Possible biochemical processes underlying the positive health effects of plant-based diets-a narrative review.Nutrients2021;13:2593 PMCID:PMC8398942

[56] Ashor AW,Mathers JC.Effect of vitamin C on endothelial function in health and disease: a systematic review and meta-analysis of randomised controlled trials.Atherosclerosis2014;235:9-20

[57] Juraschek SP,Appel LJ.Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials.Am J Clin Nutr2012;95:1079-88 PMCID:PMC3325833

[58] D’Souza MS,Ragazzo G.From fad to fact: evaluating the impact of emerging diets on the prevention of cardiovascular disease.Am J Med2020;133:1126-34

[59] Aksungar FB,Akyildiz M.Interleukin-6, C-reactive protein and biochemical parameters during prolonged intermittent fasting.Ann Nutr Metab2007;51:88-95

[60] Varady KA,Klempel MC.Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial.Nutr J2013;12:146 PMCID:PMC3833266

[61] Wang X,Liao Q.Effects of intermittent fasting diets on plasma concentrations of inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials.Nutrition2020;79-80:110974

[62] Liu Y,Sweeney G.Examining the potential of developing and implementing use of adiponectin-targeted therapeutics for metabolic and cardiovascular diseases.Front Endocrinol2019;10:842 PMCID:PMC6918867

[63] Feizollahzadeh S,Kheirouri S.Augmented plasma adiponectin after prolonged fasting during ramadan in men.Health Promot Perspect2014;4:77-81 PMCID:PMC4122042

[64] Cho Y,Kim KW.The effectiveness of intermittent fasting to reduce body mass index and glucose metabolism: a systematic review and meta-analysis.J Clin Med2019;8:1645 PMCID:PMC6832593

[65] Horne BD,May HT.Relation of routine, periodic fasting to risk of diabetes mellitus, and coronary artery disease in patients undergoing coronary angiography.Am J Cardiol2012;109:1558-62

[66] Nematy M,Rashed MM.Effects of Ramadan fasting on cardiovascular risk factors: a prospective observational study.Nutr J2012;11:69 PMCID:PMC3487759

[67] Mayra ST.Arterial stiffness and cardiometabolic health in omnivores and vegetarians: a cross-sectional pilot study.BMC Res Notes2022;15:69 PMCID:PMC8858561

[68] Zuo L,Tinsley GM,Ward E.Comparison of high-protein, intermittent fasting low-calorie diet and heart healthy diet for vascular health of the obese.Front Physiol2016;7:350 PMCID:PMC5002412

[69] Machado d’Almeida K, Ronchi Spillere S, Zuchinali P, Corrêa Souza G. Mediterranean diet and other dietary patterns in primary prevention of heart failure and changes in cardiac function markers: a systematic review.Nutrients2018;10:58 PMCID:PMC5793286

[70] Chrysohoou C,Metallinos G.Cross-sectional relationship of a Mediterranean type diet to diastolic heart function in chronic heart failure patients.Heart Vessels2012;27:576-84

[71] Papadaki A,Alonso-Gómez A.Mediterranean diet and risk of heart failure: results from the PREDIMED randomized controlled trial.Eur J Heart Fail2017;19:1179-85

[72] Varadarajan P,Fraser GE.Left ventricular diastolic abnormalities in vegetarians as compared with non-vegetarians.Br J Nutr2022;:1-28

[73] Okoshi K,Polin MAM.Influence of intermittent fasting on myocardial infarction-induced cardiac remodeling.BMC Cardiovasc Disord2019;19:126 PMCID:PMC6540428

[74] Lee KW,Ching SM,Hoo FK.Effects of vegetarian diets on blood pressure lowering: a systematic review with meta-analysis and trial sequential analysis.Nutrients2020;12:1604 PMCID:PMC7352826

[75] Barnard ND,Rembert E.A mediterranean diet and low-fat vegan diet to improve body weight and cardiometabolic risk factors: a randomized, cross-over trial.J Am Nutr Assoc2022;41:127-39

[76] de Toledo F,Bergouignan A,Michalsen A.Safety, health improvement and well-being during a 4 to 21-day fasting period in an observational study including 1422 subjects.PLoS One2019;14:e0209353

[77] Phaniendra A,Periyasamy L.Free radicals: properties, sources, targets, and their implication in various diseases.Indian J Clin Biochem2015;30:11-26 PMCID:PMC4310837

[78] Pham-Huy LA,Pham-Huy C.Free radicals, antioxidants in disease and health.Int J Biomed Sci2008;4:89 PMCID:PMC3614697

[79] Sohal RS.Role of oxidative stress and protein oxidation in the aging process.Free Radic Biol Med2002;33:37-44

[80] Mylonas C.Lipid peroxidation and tissue damage.In Vivo1999;13:295-309

[81] Brieger K,Miller FJ.Reactive oxygen species: from health to disease.Swiss Med Wkly2012;142:w13659

[82] Tahara EB,Kowaltowski AJ.Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation.Free Radic Biol Med2009;46:1283-97

[83] Beckman KB.The free radical theory of aging matures.Physiolo Rev1998;78:54781

[84] Guzik TJ,Guzik B.Coronary artery superoxide production and nox isoform expression in human coronary artery disease.Arterioscler Thromb Vasc Biol2006;26:333-9

[85] Steffen Y,Stolle K.Cigarette smoke and LDL cooperate in reducing nitric oxide bioavailability in endothelial cells via effects on both eNOS and NADPH oxidase.Nitric Oxide2012;27:176-84

[86] Giacco F.Oxidative stress and diabetic complications.Circ Res2010;107:1058-70 PMCID:PMC2996922

[87] Li H.Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease.Curr Opin Pharmacol2013;13:161-7

[88] Donato AJ,Silver AE.Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-κB.Circ Res2007;100:1659-66

[89] Rodríguez-Mañas L,Vallejo S.Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation.Aging Cell2009;8:226-38

[90] Taddei S,Ghiadoni L.Age-related reduction of NO availability and oxidative stress in humans.Hypertension2001;38:274-9

[91] Fujimoto H,Ohno M.Age-induced reduction in mitochondrial manganese superoxide dismutase activity and tolerance of macrophages against apoptosis induced by oxidized low density lipoprotein.Circ J2010;74:353-60

[92] Kattoor AJ,Palagiri D.Oxidative stress in atherosclerosis.Curr Atheroscler Rep2017;19:42

[93] Brinkley TE,Kanaya AM.Plasma oxidized low-density lipoprotein levels and arterial stiffness in older adults: the health, aging, and body composition study.Hypertension2009;53:846-52 PMCID:PMC2692957

[94] Madamanchi NR.Mitochondrial dysfunction in atherosclerosis.Circ Res2007;100:460-73

[95] Yang H,Shi MJ.Retardation of atherosclerosis by overexpression of catalase or both Cu/Zn-superoxide dismutase and catalase in mice lacking apolipoprotein E.Circ Res2004;95:1075-81

[96] Cheng F,Degreif A,Canisius A.Impact of glutathione peroxidase-1 deficiency on macrophage foam cell formation and proliferation: implications for atherogenesis.PloS one2013;8:e72063 PMCID:PMC3750037

[97] Maack C.Targeting mitochondrial oxidative stress in heart failure throttling the afterburner.J Am Coll Cardiol2011;58:83-6

[98] Dai DF,Villarin JJ.Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure.Circ Res2011;108:837-46 PMCID:PMC3785241

[99] Qin F,Lancel S.Hydrogen peroxide-mediated SERCA cysteine 674 oxidation contributes to impaired cardiac myocyte relaxation in senescent mouse heart.J Am Heart Assoc2013;2:e000184 PMCID:PMC3828801

[100] Gonzalez DR,Castellanos J,Hare JM.Impaired S-nitrosylation of the ryanodine receptor caused by xanthine oxidase activity contributes to calcium leak in heart failure.J Biol Chem2010;285:28938-45 PMCID:PMC2937920

[101] Erickson JR,Guan X.A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation.Cell2008;133:462-74 PMCID:PMC2435269

[102] Raad M,Wei J.Oxidative Stress is associated with diastolic dysfunction in women with ischemia with no obstructive coronary artery disease.J Am Heart Assoc2020;9:e015602 PMCID:PMC7660868

[103] Brand M.The efficiency and plasticity of mitochondrial energy transduction.Biochem Soc Trans2005;33:897-904

[104] Wei YH.Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging.Exp Biol Med2002;227:671-82

[105] Rodríguez-Bies E,López-Lluch G.Age-dependent effect of every-other-day feeding and aerobic exercise in ubiquinone levels and related antioxidant activities in mice muscle.J Gerontol Ser A2015;70:33-43

[106] Hagopian K,Ram JJ,Weindruch R.Long-term calorie restriction reduces proton leak and hydrogen peroxide production in liver mitochondria.Am J Physiol Endocrinol Metab2005;288:E674-84

[107] Bevilacqua L,Hagopian K,Harper ME.Effects of short-and medium-term calorie restriction on muscle mitochondrial proton leak and reactive oxygen species production.Am J Physiol Endocrinol Metab2004;286:E852-E61

[108] Redman LM,Burton JH,Il’yasova D.Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging.Cell Metab2018;27:805-815.e4 PMCID:PMC5886711

[109] Gredilla R,Lopez-Torres M.Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart.FASEB J2001;15:1589-91

[110] López-Lluch G,Jones B.Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency.Proc Natl Acad Sci USA2006;103:1768-73 PMCID:PMC1413655

[111] Baker DJ,Krause DJ.No decline in skeletal muscle oxidative capacity with aging in long-term calorically restricted rats: effects are independent of mitochondrial DNA integrity.J Gerontol Ser A2006;61:675-84

[112] Civitarese AE,Heilbronn LK.Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.PLoS Med2007;4:e76 PMCID:PMC1808482

[113] Nisoli E,Cardile A.Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS.Science2005;310:314-7

[114] Rippe C,Connell M,Donato A.Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress.Aging cell2010;9:304-12 PMCID:PMC2894368

[115] Faulks SC,Else PL.Calorie restriction in mice: effects on body composition, daily activity, metabolic rate, mitochondrial reactive oxygen species production, and membrane fatty acid composition.J Gerontol A Biol Sci Med Sci2006;61:781-94

[116] Pieri C,Marcheselli F.Food restriction in female Wistar rats: V. Lipid peroxidation and antioxidant enzymes in the liver.Arch Gerontol Geriatr1992;14:93-9

[117] Il’yasova D,Bhapkar M.Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2-isoprostanes: The CALERIE 2 randomized clinical trial.Aging Cell2018;17:e12719 PMCID:PMC5847862

[118] Harvie MN,Mattson MP.The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women.Int J Obes2011;35:714-27 PMCID:PMC3017674

[119] Fulco M,Zhao P.Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt.Dev Cell2008;14:661-73 PMCID:PMC2431467

[120] Castello L,Maina M.Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation.Free Radic Biol Med2010;48:47-54

[121] Johnson JB,Cutler RG.Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma.Free Radic Biol Med2007;42:665-74 PMCID:PMC1859864

[122] Cienfuegos S,Kalam F.Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity.Cell Metab2020;32:366-378.e3 PMCID:PMC9407646

[123] Guo Y,Ye Y,Fan J.Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients.J Clin Endocrinol Metab2021;106:64-79

[124] Sutton EF,Early KS,Ravussin E.Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes.Cell Metab2018;27:1212-21.e3 PMCID:PMC5990470

[125] Yuzefovych L,Rachek L.Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress.Am J Physiol Endocrinol Metab2010;299:E1096-105 PMCID:PMC3006254

[126] Eisenberg T,Schroeder S.Cardioprotection and lifespan extension by the natural polyamine spermidine.Nat Med2016;22:1428-38 PMCID:PMC5806691

[127] Marin C,Ramirez R.Mediterranean diet reduces senescence-associated stress in endothelial cells.Age2012;34:1309-16 PMCID:PMC3528364

[128] Cicero AF,López-Sabater MC.Changes in LDL fatty acid composition as a response to olive oil treatment are inversely related to lipid oxidative damage: The Eurolive study.J Am Coll Nutr2008;27:314-20

[129] Visioli F,Gall C.Antioxidant and other biological activities of phenols from olives and olive oil.Med Res Rev2002;22:65-75

[130] Kwon B,Querfurth HW.Oleate prevents palmitate-induced mitochondrial dysfunction, insulin resistance and inflammatory signaling in neuronal cells.Biochim Biophys Acta2014;1843:1402-13

[131] Fitó M,Corella D.Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial.Arch Int Med2007;167:1195-203

[132] Huguenin GV,Moreira AS.Improvement of antioxidant status after Brazil nut intake in hypertensive and dyslipidemic subjects.Nutr J2015;14:54 PMCID:PMC4477321

[133] Ghavipour M,Ghorbani M.Tomato juice consumption improves blood antioxidative biomarkers in overweight and obese females.Clin Nutr2015;34:805-9

[134] Gylling H,Turley S.Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease.Atherosclerosis2014;232:346-60

[135] Bumrungpert A,Phosat C.Rice bran oil containing gamma-oryzanol improves lipid profiles and antioxidant status in hyperlipidemic subjects: a randomized double-blind controlled trial.J Altern Complement Med2019;25:353-8

[136] Asemi Z,Tabassi Z,Sabihi SS.Effects of DASH diet on lipid profiles and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome: a randomized clinical trial.Nutrition2014;30:1287-93

[137] Rahbar AR,Islam MS.Comparative effects of red and white grapes on oxidative markers and lipidemic parameters in adult hypercholesterolemic humans.Food Funct2015;6:1992-8

[138] Sohrab G,Sotoudeh G.Effects of pomegranate juice consumption on oxidative stress in patients with type 2 diabetes: a single-blind, randomized clinical trial.Int J Food Sci Nutr2017;68:249-55

[139] Jiang S,Li C.Dietary regulation of oxidative stress in chronic metabolic diseases.Foods2021;10:1854 PMCID:PMC8391153

[140] Tammen SA,Choi SW.Epigenetics: the link between nature and nurture.Mol Aspects Med2013;34:753-64 PMCID:PMC3515707

[141] Ho DH.Transgenerational epigenetics: the role of maternal effects in cardiovascular development.Integr Comp Biol2014;54:43-51 PMCID:PMC4133574

[142] Cooper WN,Owens S.DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: results of a pilot randomized controlled trial.FASEB J2012;26:1782-90

[143] Zhang W,Qu J.Epigenetic modifications in cardiovascular aging and diseases.Circ Res2018;123:773-86

[144] Prasher D,Singh RB.The impact of epigenetics on cardiovascular disease.Biochem Cell Biol2020;98:12-22

[145] Cao Y,Liu M.Impact of epigenetics in the management of cardiovascular disease: a review.Eur Rev Med Pharmacol Sci2014;18:3097-104.

[146] Jones PA.Functions of DNA methylation: islands, start sites, gene bodies and beyond.Nat Rev Genet2012;13:484-92

[147] Shi Y,Huang S.Epigenetic regulation in cardiovascular disease: mechanisms and advances in clinical trials.Signal Transduct Target Ther2022;7:200 PMCID:PMC9233709

[148] Tabaei S.DNA methylation abnormalities in atherosclerosis.Artif Cells Nanomed Biotechnol2019;47:2031-41

[149] Horvath S.DNA methylation-based biomarkers and the epigenetic clock theory of ageing.Nat Rev Genet2018;19:371-84

[150] Yamada Y,Oguri M.Identification of novel hyper- or hypomethylated CpG sites and genes associated with atherosclerotic plaque using an epigenome-wide association study.Int J Mol Med2018;41:2724-32 PMCID:PMC5846673

[151] Zhang Y.Role of DNA methylation in cardiovascular diseases.Clin Exp Hypertens2016;38:261-7

[152] Han P,Yang J.Epigenetic response to environmental stress: assembly of BRG1-G9a/GLP-DNMT3 repressive chromatin complex on Myh6 promoter in pathologically stressed hearts.Biochim Biophys Acta2016;1863:1772-81 PMCID:PMC7397641

[153] Li W,Huang R.Association of lipid metabolism-related gene promoter methylation with risk of coronary artery disease.Mol Biol Rep2022;49:9373-8

[154] Frazier-Wood AC,Absher DM.Methylation at CPT1A locus is associated with lipoprotein subfraction profiles.J Lipid Res2014;55:1324-30 PMCID:PMC4076093

[155] Lei H,Sun K.The role and molecular mechanism of epigenetics in cardiac hypertrophy.Heart Fail Rev2021;26:1505-14

[156] Gilsbach R,Grüning BA.Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease.Nat Commun2014;5:5288 PMCID:PMC4220495

[157] Zheng Y,Hwang SJ.Association of cardiovascular health through young adulthood with genome-wide dna methylation patterns in midlife: the cardia study.Circulation2022;146:94-109 PMCID:PMC9348746

[158] Tessarz P.Histone core modifications regulating nucleosome structure and dynamics.Nat Rev Mol Cell Biol2014;15:703-8

[159] Zhang Y,Jia J.Overview of histone modification.Adv Exp Med Biol2021;1283:1-16

[160] Tang H,Shang C,Liu J.Epigenetic regulation in pathology of atherosclerosis: a novel perspective.Front Genet2021;12:810689 PMCID:PMC8714670

[161] Groh L,Joosten LAB,Riksen NP.Monocyte and macrophage immunometabolism in atherosclerosis.Semin Immunopathol2018;40:203-14 PMCID:PMC5809534

[162] Kim GR,Kim HS.Histone deacetylase and GATA-binding factor 6 regulate arterial remodeling in angiotensin II-induced hypertension.J Hypertens2016;34:2206-19

[163] Jeong MY,Wennersten SA.Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism.Sci Transl Med2018;2018;10 PMCID:PMC5908215

[164] Zhang QJ,Wang L,Hill JA.The histone trimethyllysine demethylase JMJD2A promotes cardiac hypertrophy in response to hypertrophic stimuli in mice.J Clin Invest2011;121:2447-56 PMCID:PMC3104772

[165] Mushtaq I,Ali T,Murtaza I.An overview of non-coding RNAs and cardiovascular system.Adv Exp Med Biol2020;1229:3-45

[166] Das S,Dimmeler S.Noncoding RNAs in cardiovascular disease: current knowledge, tools and technologies for investigation, and future directions: a scientific statement from the american heart association.Circ Genom Precis Med2020;13:e000062

[167] Ghebre YT,Wong WT.Vascular aging: implications for cardiovascular disease and therapy.Transl Med2016;6:183 PMCID:PMC5602592

[168] Wang J.The function of miRNA in cardiac hypertrophy.Cell Mol Life Sci2012;69:3561-70 PMCID:PMC3474911

[169] Zhao C,Li J.Non-coding RNAs and cardiac aging.Adv Exp Med Biol2020;1229:247-58

[170] Huang ZP,Seok HY.MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress.Circ Res2013;112:1234-43 PMCID:PMC3720677

[171] Amenyah SD,Strain JJ.Nutritional epigenomics and age-related disease.Curr Dev Nutr2020;4:nzaa097 PMCID:PMC7335360

[172] Parrillo L,Raciti GA.Hoxa5 undergoes dynamic DNA methylation and transcriptional repression in the adipose tissue of mice exposed to high-fat diet.Int J Obes2016;40:929-37

[173] Ciccarone F,Ioannilli L.High dietary fat intake affects DNA methylation/hydroxymethylation in mouse heart: epigenetic hints for obesity-related cardiac dysfunction.Mol Nutr Food Res2019;63:e1800970

[174] Jacobsen SC,Bork-Jensen J.Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men.Diabetologia2012;55:3341-9

[175] Perfilyev A,Gillberg L.Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial.Am J Clin Nutr2017;105:991-1000

[176] Osaka M,Aoyama J,Ishigami A.High-fat diet enhances neutrophil adhesion in LDLR-null mice via hypercitrullination of histone H3.JACC Basic Transl Sci2021;6:507-23 PMCID:PMC8246031

[177] Jung JK,Jang G,Kim I.Inhibition of HDACs (histone deacetylases) ameliorates high-fat diet-induced hypertension through restoration of the MsrA (methionine sulfoxide reductase a)/hydrogen sulfide axis.Hypertension2021;78:1103-15

[178] Guedes EC,Lino CA.MicroRNA expression signature is altered in the cardiac remodeling induced by high fat diets.J Cell Physiol2016;231:1771-83

[179] Dasinger JH,Abais-Battad JM.Epigenetic modifications in T cells: the role of dna methylation in salt-sensitive hypertension.Hypertension2020;75:372-82 PMCID:PMC7058976

[180] Gao P,Li L.Salt-induced hepatic inflammatory memory contributes to cardiovascular damage through epigenetic modulation of SIRT3.Circulation2022;145:375-91

[181] Amara VR,Tikoo K.Dysregulation of microRNAs and renin-angiotensin system in high salt diet-induced cardiac dysfunction in uninephrectomized rats.PLoS One2017;12:e0180490 PMCID:PMC5519030

[182] Kidambi S,Yang C.Dietary sodium restriction results in tissue-specific changes in dna methylation in humans.Hypertension2021;78:434-46 PMCID:PMC9299531

[183] Chen L,Dong Y,Harshfield GA.Sodium reduction, miRNA profiling and CVD risk in untreated hypertensives: a randomized, double-blind, placebo-controlled trial.Sci Rep2018;8:12729 PMCID:PMC6109065

[184] Ma J,Braun KVE.Whole blood DNA methylation signatures of diet are associated with cardiovascular disease risk factors and all-cause mortality.Circ Genom Precis Med2020;13:e002766 PMCID:PMC7442697

[185] Kim Y,Joehanes R.Higher diet quality relates to decelerated epigenetic aging.Am J Clin Nutr2022;115:163-70 PMCID:PMC8755029

[186] Do WL,Costeira R.Epigenome-wide association study of diet quality in the Women’s Health Initiative and TwinsUK cohort.Int J Epidemiol2021;50:675-84 PMCID:PMC8128469

[187] Arpón A,Milagro FI.Adherence to mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells.J Physiol Biochem2016;73:445-55

[188] Yubero-Serrano EM,Garcia-Rios A.Mediterranean diet and endothelial function in patients with coronary heart disease: An analysis of the CORDIOPREV randomized controlled trial.PLoS Med2020;17:e1003282 PMCID:PMC7480872

[189] Marques-Rocha JL,Mansego ML,Bressan J.Expression of inflammation-related miRNAs in white blood cells from subjects with metabolic syndrome after 8 wk of following a Mediterranean diet-based weight loss program.Nutrition2016;32:48-55

[190] Arpón A,Razquin C.Impact of consuming extra-virgin olive oil or nuts within a mediterranean diet on DNA methylation in peripheral white blood cells within the PREDIMED-navarra randomized controlled trial: a role for dietary lipids.Nutrients2017;10:15 PMCID:PMC5793243

[191] Daimiel L,Valls RM.Impact of phenol-enriched virgin olive oils on the postprandial levels of circulating micrornas related to cardiovascular disease.Mol Nutr Food Res2020;64:e2000049 PMCID:PMC7507201

[192] Fabiani R,Rosignoli P.Epigenetic modifications induced by olive oil and its phenolic compounds: a systematic review.Molecules2021;26:273 PMCID:PMC7826507

[193] Ramos-Lopez O,Riezu-Boj JI.Epigenetic signatures underlying inflammation: an interplay of nutrition, physical activity, metabolic diseases, and environmental factors for personalized nutrition.Inflamm Res2021;70:29-49 PMCID:PMC7684853

[194] Castañer O,Covas MI.In vivo transcriptomic profile after a Mediterranean diet in high-cardiovascular risk patients: a randomized controlled trial.Am J Clin Nutr2013;98:845-53

[195] Mattson MP,Harvie M.Impact of intermittent fasting on health and disease processes.Ageing Res Rev2017;39:46-58 PMCID:PMC5411330

[196] Ruan HB.Ketone bodies as epigenetic modifiers.Curr Opin Clin Nutr Metab Care2018;21:260-6

[197] Asif S,Mulvihill EE.Understanding Dietary Intervention-Mediated Epigenetic Modifications in Metabolic Diseases.Front Genet2020;11:590369 PMCID:PMC7593700

[198] Saini SK,Saini M,Leeuwenburgh C.Time-restricted eating regimen differentially affects circulatory miRNA expression in older overweight adults.Nutrients2022;14:1843 PMCID:PMC9100641