Ageing is a multifactorial process associated with reduced function and increased risk of morbidity and mortality. Recently, nine cellular and molecular hallmarks of ageing have been identified, which characterise the ageing process, and collectively, may be key determinants of the ageing trajectory. These include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intercellular communication. Healthier dietary patterns reduce the risk of age-related diseases and increase longevity and may influence positively one or more of these hallmarks. The Mediterranean dietary pattern (MedDiet) is a plant-based eating pattern that was typical of countries such as Greece, Spain, and Italy pre-globalisation of the food system and which is associated with better health during ageing. Here we review the potential effects of a MedDiet on each of the nine hallmarks of ageing, and provide evidence that the MedDiet as a whole, or individual elements of this dietary pattern, may influence each hallmark positively—effects which may contribute to the beneficial effects of this dietary pattern on age-related disease risk and longevity. We also highlight potential avenues for future research.
This is a preview of subscription content, access via your institution
Open Access articles citing this article.
Dietary nitrate and population health: a narrative review of the translational potential of existing laboratory studies
BMC Sports Science, Medicine and Rehabilitation Open Access 07 June 2021
Subscribe to Journal
Get full journal access for 1 year
only $9.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153:1194–217.
Niccoli T, Partridge L. Ageing as a risk factor for disease. Curr Biol. 2012;22:R741–52.
Mathers JC. Impact of nutrition on the ageing process. Br J Nutr. 2015;113:S18–22.
Stevenson EJ, Shannon OM, Minihane AM, Adamson A, Burns A, Hill T, et al. NuBrain: UK consortium for optimal nutrition for healthy brain ageing. Nutr Bull. 2020;45:223–9.
Bach-Faig A, Berry EM, Lairon D, Reguant J, Trichopoulou A, Dernini S, et al. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr. 2011;14:2274–84.
Shannon OM, Stephan BCM, Granic A, Lentjes M, Hayat S, Mulligan A, et al. Mediterranean diet adherence and cognitive function in older UK adults: the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk) Study. Am J Clin Nutr. 2019;110:938–48.
Shannon OM, Stephan BCM, Minihane A-M, Mathers JC, Siervo M. Nitric oxide boosting effects of the Mediterranean diet: a potential mechanism of action. J Gerontol A Biol Sci Med Sci. 2018;73:902–4.
Hernández JM, Rentero MPZ. Bioactive compounds contained in Mediterranean Diet and their effects on neurodegenerative diseases. In: Shiomi N, editor. Current topics on superfoods. London: IntechOpen; 2018. pp. 13–32.
Tosti V, Bertozzi B, Fontana L. Health benefits of the Mediterranean diet: metabolic and molecular mechanisms. J Gerontol A Biol Sci Med Sci. 2018;73:318–26.
Del Rio D, Costa LG, Lean MEJ, Crozier A. Polyphenols and health: what compounds are involved? Nutr Metab Cardiovasc Dis. 2010;20:1–6.
Buttriss JL, Stokes CS. Dietary fibre and health: an overview. Nutr Bull. 2008;33:186–200.
Swanson D, Block R, Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr. 2012;3:1–7.
Siervo M, Scialò F, Shannon OM, Stephan BCM, Ashor AW. Does dietary nitrate say NO to cardiovascular ageing? Current evidence and implications for research. Proc Nutr Soc. 2018;77:112–23.
Ashor AW, Shannon OM, Werner A-D, Scialo F, Gilliard CN, Cassel KS, et al. Effects of inorganic nitrate and vitamin C co-supplementation on blood pressure and vascular function in younger and older healthy adults: a randomised double-blind crossover trial. Clin Nutr. 2019;39:708–17.
Estruch R, Ros E, Salas-Salvadó J, Covas M-I, Corella D, Arós F, et al. Primary prevention of cardiovascular disease with a Mediterranean Diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378:e34.
Salas-Salvadó J, Bulló M, Babio N, Martínez-González MÁ, Ibarrola-Jurado N, Basora J, et al. Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial. Diabetes Care. 2011;34:14–9.
Petersson SD, Philippou E. Mediterranean diet, cognitive function, and dementia: a systematic review of the evidence. Adv Nutr. 2016;7:889–904.
Schwingshackl L, Schwedhelm C, Galbete C, Hoffmann G. Adherence to Mediterranean diet and risk of cancer: An updated systematic review and meta-analysis. Nutrients. 2017;9:1063.
Lasheras C, Fernandez S, Patterson AM. Mediterranean diet and age with respect to overall survival in institutionalized, nonsmoking elderly people. Am J Clin Nutr. 2000;71:987–92.
Trichopoulou A, Orfanos P, Norat T, Bueno-de-Mesquita B, Ocké MC, Peeters PH, et al. Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study. BMJ. 2005;330:991.
Soltani S, Jayedi A, Shab-Bidar S, Becerra-Tomás N, Salas-Salvadó J. Adherence to the Mediterranean Diet in relation to all-cause mortality: A systematic review and dose-response meta-analysis of prospective cohort studies. Adv Nutr. 2019;10:1029–39.
Aguilera A, Gómez-González B. Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet. 2008;9:204–17.
Corella D, Ordovas J, Sorli J, Asensio E, Ortega C, Carrasco P, et al. Effect of the Mediterranean diet on DNA methylation of selected genes in the PREDIMED-Valencia intervention trial. FASEB J. 2015;29:LB242.
Herrera-Marcos LV, Lou-Bonafonte JM, Arnal C, Navarro MA, Osada J. Transcriptomics and the Mediterranean diet: a systematic review. Nutrients. 2017;9:472.
Ungvari Z, Bagi Z, Feher A, Recchia FA, Sonntag WE, Pearson K, et al. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol. 2010;299:H18–24.
Arpón A, Riezu-Boj JI, Milagro FI, Marti A, Razquin C, Martínez-González MA, et al. Adherence to Mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells. J Physiol Biochem. 2016;73:445–55.
Kaneko K, Akuta T, Sawa T, Kim HW, Fujii S, Okamoto T, et al. Mutagenicity of 8-nitroguanosine, a product of nitrative nucleoside modification by reactive nitrogen oxides, in mammalian cells. Cancer Lett. 2008;262:239–47.
Zhang Y, Yuan F, Wu X, Wang M, Rechkoblit O, Taylor J-S, et al. Error-free and error-prone lesion bypass by human DNA polymerase κ in vitro. Nucleic Acids Res. 2000;28:4138–46.
Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J. Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem. 2004;266:37–56.
Urquiaga I, Strobel P, Perez D, Martinez C, Cuevas A, Castillo O, et al. Mediterranean diet and red wine protect against oxidative damage in young volunteers. Atherosclerosis. 2010;211:694–9.
Vilahur G, Cubedo J, Padró T, Casaní L, Mendieta G, González A, et al. Intake of cooked tomato sauce preserves coronary endothelial function and improves apolipoprotein A-I and apolipoprotein J protein profile in high-density lipoproteins. Transl Res. 2015;166:44–56.
Erol Ö, Arda N, Erdem G. Phenols of virgin olive oil protects nuclear DNA against oxidative damage in HeLa cells. Food Chem Toxicol. 2012;50:3475–9.
Rangel-Zuñiga OA, Haro C, Tormos C, Perez-Martinez P, Delgado-Lista J, Marin C, et al. Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage. Eur J Nutr. 2017;56:1597–607.
Calcabrini C, De Bellis R, Mancini U, Cucchiarini L, Stocchi V, Potenza L. Protective effect of juglans regia L. walnut extract against oxidative DNA damage. Plant Foods Hum Nutr. 2017;72:192–7.
Quiles JL, Ochoa JJ, Ramirez-Tortosa C, Battino M, Huertas JR, Martín Y, et al. Dietary fat type (virgin olive vs. sunflower oils) affects age-related changes in DNA double-strand-breaks, antioxidant capacity and blood lipids in rats. Exp Gerontol. 2004;39:1189–98.
Saieva C, Peluso M, Palli D, Cellai F, Ceroti M, Selvi V, et al. Dietary and lifestyle determinants of malondialdehyde DNA adducts in a representative sample of the Florence City population. Mutagenesis. 2016;31:475–80.
von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci. 2002;27:339–44.
Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361:2353–65.
Boonekamp JJ, Simons MJP, Hemerik L, Verhulst S. Telomere length behaves as biomarker of somatic redundancy rather than biological age. Aging Cell. 2013;12:330–2.
Astuti Y, Wardhana A, Watkins J, Wulaningsih W. PILAR Research Network. Cigarette smoking and telomere length: a systematic review of 84 studies and meta-analysis. Environ Res. 2017;158:480–9.
Arsenis NC, You T, Ogawa EF, Tinsley GM, Zuo L. Physical activity and telomere length: impact of aging and potential mechanisms of action. Oncotarget. 2017;8:45008–19.
Meinilä J, Perälä M-M, Kautiainen H, Männistö S, Kanerva N, Shivappa N, et al. Healthy diets and telomere length and attrition during a 10-year follow-up. Eur J Clin Nutr. 2019;73:1352–60.
Boccardi V, Esposito A, Rizzo MR, Marfella R, Barbieri M, Paolisso G. Mediterranean diet, telomere maintenance and health status among elderly. PLoS ONE. 2013;8:e62781.
Crous-Bou M, Fung TT, Prescott J, Julin B, Du M, Sun Q, et al. Mediterranean diet and telomere length in Nurses’ Health Study: population based cohort study. BMJ. 2014;349:g6674.
Gu Y, Honig LS, Schupf N, Lee JH, Luchsinger JA, Stern Y, et al. Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population. Age. 2015;37:24.
García-Calzón S, Martínez-González MA, Razquin C, Corella D, Salas-Salvadó J, Martínez JA, et al. Pro12Ala polymorphism of the PPARγ2 gene interacts with a Mediterranean diet to prevent telomere shortening in the PREDIMED-NAVARRA randomized trial. Circ Genom Precis Med. 2015;8:91–9.
Gomez-Delgado F, Delgado-Lista J, Lopez-Moreno J, Rangel-Zuñiga OA, Alcala-Diaz JF, Leon-Acuña A, et al. Telomerase RNA component genetic variants interact with the Mediterranean diet modifying the inflammatory status and its relationship with aging: CORDIOPREV study. J Gerontol A Biol Sci Med Sci. 2018;73:327–32.
García-Calzón S, Zalba G, Ruiz-Canela M, Shivappa N, Hébert JR, Martínez JA, et al. Dietary inflammatory index and telomere length in subjects with a high cardiovascular disease risk from the PREDIMED-NAVARRA study: cross-sectional and longitudinal analyses over 5 y. Am J Clin Nutr. 2015;102:897–904.
García-Calzón S, Martínez-González MA, Razquin C, Arós F, Lapetra J, Martínez JA, et al. Mediterranean diet and telomere length in high cardiovascular risk subjects from the PREDIMED-NAVARRA study. Clin Nutr. 2016;35:1399–405.
Cora’ D, Re A, Caselle M, Bussolino F. MicroRNA-mediated regulatory circuits: outlook and perspectives. Phys Biol. 2017;14:045001.
Pal S, Tyler JK. Epigenetics and aging. Sci Adv. 2016;2:e1600584.
Mathers JC, Strathdee G, Relton CL. Induction of epigenetic alterations by dietary and other environmental factors. Adv Genet. 2010;71:3–39.
Mathers JC. Session 2: personalised nutrition. Epigenomics: a basis for understanding individual differences? Proc Nutr Soc. 2008;67:390–4.
Park JH, Yoo Y, Park YJ. Epigenetics: linking nutrition to molecular mechanisms in aging. Prev Nutr Food Sci. 2017;22:81–9.
Lisanti S, Omar WAW, Tomaszewski B, Prins SD, Jacobs G, Koppen G, et al. Comparison of methods for quantification of global DNA methylation in human cells and tissues. PLoS ONE. 2013;8:e79044.
Muka T, Koromani F, Portilla E, O’Connor A, Bramer WM, Troup J, et al. The role of epigenetic modifications in cardiovascular disease: a systematic review. Int J Cardiol. 2016;212:174–83.
Cardelli M. The epigenetic alterations of endogenous retroelements in aging. Mech Ageing Dev. 2018;174:30–46.
Agodi A, Barchitta M, Quattrocchi A, Maugeri A, Canto C, Marchese AE, et al. Low fruit consumption and folate deficiency are associated with LINE-1 hypomethylation in women of a cancer-free population. Genes Nutr. 2015;10:480.
Marques-Rocha JL, Milagro FI, Mansego ML, Zulet MA, Bressan J, Martínez JA. 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. Nutrition. 2016;32:48–55.
Tang B, Lei B, Qi G, Liang X, Tang F, Yuan S, et al. MicroRNA-155-3p promotes hepatocellular carcinoma formation by suppressing FBXW7 expression. J Exp Clin Cancer Res. 2016;35:93.
Spolverini A, Fuchs G, Bublik DR, Oren M. let-7b and let-7c microRNAs promote histone H2B ubiquitylation and inhibit cell migration by targeting multiple components of the H2B deubiquitylation machinery. Oncogene. 2017;36:5819–28.
Ma J, Rebholz CM, Braun KVE, Reynolds LM, Aslibekyan S, Xia R, et al. Whole blood DNA methylation signatures of diet are associated with cardiovascular disease risk factors and all-cause mortality. Circ Genomic Precis Med. 2020. https://doi.org/10.1161/CIRCGEN.119.002766.
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:R115.
Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018;19:371–84.
Horvath S, Erhart W, Brosch M, Ammerpohl O, von Schönfels W, Ahrens M, et al. Obesity accelerates epigenetic aging of human liver. Proc Natl Acad Sci USA. 2014;111:15538–43.
Quach A, Levine ME, Tanaka T, Lu AT, Chen BH, Ferrucci L, et al. Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging. 2017;9:419–46.
Gensous N, Garagnani P, Santoro A, Giuliani C, Ostan R, Fabbri C, et al. One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project. GeroScience. 2020;42:687–701.
Labbadia J, Morimoto RI. The biology of proteostasis in aging and disease. Annu Rev Biochem. 2015;84:435–64.
Yerbury JJ, Ooi L, Dillin A, Saunders DN, Hatters DM, Beart PM, et al. Walking the tightrope: proteostasis and neurodegenerative disease. J Neurochem. 2016;137:489–505.
Henning RH, Brundel BJJM. Proteostasis in cardiac health and disease. Nat Rev Cardiol. 2017;14:637–53.
Román GC, Jackson RE, Reis J, Román AN, Toledo JB, Toledo E. Extra-virgin olive oil for potential prevention of Alzheimer disease. Rev Neurol. 2019;175:705–23.
Fernández del Río L, Gutiérrez-Casado E, Varela-López A, Villalba JM. Olive oil and the hallmarks of aging. Molecules. 2016;21:163.
Rigacci S, Miceli C, Nediani C, Berti A, Cascella R, Pantano D, et al. Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight. Oncotarget. 2015;6:35344–57.
Abuznait AH, Qosa H, Busnena BA, El Sayed KA, Kaddoumi A. Olive-oil-derived oleocanthal enhances β-amyloid clearance as a potential neuroprotective mechanism against Alzheimer’s disease: in vitro and in vivo studies. ACS Chem Neurosci. 2013;4:973–82.
Kirkwood TBL. Evolution of ageing. Nature. 1977;270:301–4.
Kirkwood TB, Holliday R. The evolution of ageing and longevity. Proc R Soc Lond B Biol Sci. 1979;205:531–46.
Templeman NM, Murphy CT. Regulation of reproduction and longevity by nutrient-sensing pathways. J Cell Biol. 2018;217:93–106.
de Lucia C, Murphy T, Steves CJ, Dobson RJB, Proitsi P, Thuret S. Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence. Commun Biol. 2020;3:1–17.
Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang RA. C. elegans mutant that lives twice as long as wild type. Nature. 1993;366:461–4.
Puig O, Tjian R. Transcriptional feedback control of insulin receptor by dFOXO/FOXO1. Genes Dev. 2005;19:2435–46.
van der Horst A, Burgering BMT. Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol. 2007;8:440–50.
van Heemst D. Insulin, IGF-1 and longevity. Aging Dis. 2010;1:147–57.
Calnan DR, Brunet A. The FoxO code. Oncogene. 2008;27:2276–88.
Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature. 2013;493:338–45.
Alers S, Löffler AS, Wesselborg S, Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol. 2012;32:2–11.
Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature. 2005;434:113–8.
Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325:201–4.
Vasto S, Buscemi S, Barera A, Carlo MD, Accardi G, Caruso C. Mediterranean diet and healthy ageing: a Sicilian perspective. Gerontology. 2014;60:508–18.
Fontana L, Adelaiye RM, Rastelli AL, Miles KM, Ciamporcero E, Longo VD, et al. Dietary protein restriction inhibits tumor growth in human xenograft models. Oncotarget. 2013;4:2451–61.
Kazemi A, Speakman JR, Soltani S, Djafarian K. Effect of calorie restriction or protein intake on circulating levels of insulin like growth factor I in humans: a systematic review and meta-analysis. Clin Nutr. 2020;39:1705–16.
Runchey SS, Pollak MN, Valsta LM, Coronado GD, Schwarz Y, Breymeyer KL, et al. Glycemic load effect on fasting and post-prandial serum glucose, insulin, IGF-1 and IGFBP-3 in a randomized, controlled feeding study. Eur J Clin Nutr. 2012;66:1146–52.
Di Bona D, Accardi G, Virruso C, Candore G, Caruso C. Association between genetic variations in the insulin/insulin-like growth factor (Igf-1) signaling pathway and longevity: a systematic review and meta-analysis. Curr Vasc Pharmacol. 2014;12:674–81.
de Lucia C, Murphy T, Thuret S. Emerging molecular pathways governing dietary regulation of neural stem cells during aging. Front Physiol. 2017;8:17.
Menendez JA, Joven J, Aragonès G, Barrajón-Catalán E, Beltrán-Debón R, Borrás-Linares I, et al. Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil. Cell Cycle. 2013;12:555–78.
Jung CH, Ro S-H, Cao J, Otto NM, Kim D-H. mTOR regulation of autophagy. FEBS Lett. 2010;584:1287–95.
Lee IH, Cao L, Mostoslavsky R, Lombard DB, Liu J, Bruns NE, et al. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc Natl Acad Sci USA. 2008;105:3374–9.
Russo MA, Sansone L, Polletta L, Runci A, Rashid MM, De Santis E, et al. Sirtuins and resveratrol-derived compounds: a model for understanding the beneficial effects of the Mediterranean diet. Endocr Metab Immune Disord Drug Targets. 2014;14:300–8.
McBride HM, Neuspiel M, Wasiak S. Mitochondria: more than just a powerhouse. Curr Biol. 2006;16:R551–60.
Hekimi S, Lapointe J, Wen Y. Taking a ‘good’ look at free radicals in the aging process. Trends Cell Biol. 2011;21:569–76.
Park J-S, Davis RL, Sue CM. Mitochondrial dysfunction in Parkinson’s disease: New mechanistic insights and therapeutic perspectives. Curr Neurol Neurosci Rep. 2018;18:21.
Birnbaum JH, Wanner D, Gietl AF, Saake A, Kündig TM, Hock C, et al. Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-β and tau pathology in iPSC-derived neurons from sporadic Alzheimer’s disease patients. Stem Cell Res. 2018;27:121–30.
Varela-Lopez A, Pérez-López MP, Ramirez-Tortosa CL, Battino M, Granados-Principal S, Ramirez-Tortosa MDC, et al. Gene pathways associated with mitochondrial function, oxidative stress and telomere length are differentially expressed in the liver of rats fed lifelong on virgin olive, sunflower or fish oils. J Nutr Biochem. 2018;52:36–44.
Amel N, Wafa T, Samia D, Yousra B, Issam C, Cheraif I, et al. Extra virgin olive oil modulates brain docosahexaenoic acid level and oxidative damage caused by 2,4-Dichlorophenoxyacetic acid in rats. J Food Sci Technol. 2016;53:1454–64.
Schaffer S, Podstawa M, Visioli F, Bogani P, Müller WE, Eckert GP. Hydroxytyrosol-rich olive mill wastewater extract protects brain cells in vitro and ex vivo. J Agric Food Chem. 2007;55:5043–9.
Sun W, Wang X, Hou C, Yang L, Li H, Guo J, et al. Oleuropein improves mitochondrial function to attenuate oxidative stress by activating the Nrf2 pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats. Neuropharmacology. 2017;113:556–66.
Peng Y, Hou C, Yang Z, Li C, Jia L, Liu J, et al. Hydroxytyrosol mildly improve cognitive function independent of APP processing in APP/PS1 mice. Mol Nutr Food Res. 2016;60:2331–42.
Afshordel S, Hagl S, Werner D, Röhner N, Kögel D, Bazan NG, et al. Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging-impact of Bcl-2 and NPD-1 like metabolites. Prostaglandins Leukot Essent Fat Acids. 2015;92:23–31.
Johnson ML, Lalia AZ, Dasari S, Pallauf M, Fitch M, Hellerstein MK, et al. Eicosapentaenoic acid but not docosahexaenoic acid restores skeletal muscle mitochondrial oxidative capacity in old mice. Aging Cell. 2015;14:734–43.
Lalia AZ, Dasari S, Robinson MM, Abid H, Morse DM, Klaus KA, et al. Influence of omega-3 fatty acids on skeletal muscle protein metabolism and mitochondrial bioenergetics in older adults. Aging. 2017;9:1096–129.
Markoski MM, Garavaglia J, Oliveira A, Olivaes J, Marcadenti A. Molecular properties of red wine compounds and cardiometabolic benefits. Nutr Metab Insights. 2016;9:51–7.
Qiu L, Luo Y, Chen X. Quercetin attenuates mitochondrial dysfunction and biogenesis via upregulated AMPK/SIRT1 signaling pathway in OA rats. Biomed Pharmacother. 2018;103:1585–91.
Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127:1109–22.
Markus MA, Morris BJ. Resveratrol in prevention and treatment of common clinical conditions of aging. Clin Interv Aging. 2008;3:331–9.
Putti R, Sica R, Migliaccio V, Lionetti L. Diet impact on mitochondrial bioenergetics and dynamics. Front Physiol. 2015;6:109.
von Zglinicki T, Wan T, Miwa S. Senescence in post-mitotic cells: a driver of aging? Antioxid Redox Signal. 2020. https://doi.org/10.1089/ars.2020.8048.
Collado M, Blasco MA, Serrano M. Cellular senescence in cancer and aging. Cell. 2007;130:223–33.
Tchkonia T, Zhu Y, van Deursen J, Campisi J, Kirkland JL. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J Clin Investig. 2013;123:966–72.
Song S, Lam EW-F, Tchkonia T, Kirkland JL, Sun Y. Senescent cells: emerging targets for human aging and age-related diseases. Trends Biochem Sci. 2020;45:578–92.
Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, et al. Naturally occurring p16 Ink4a -positive cells shorten healthy lifespan. Nature. 2016;530:184–9.
Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24:1246–56.
Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY, et al. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis. 2011;218:44–52.
Medina-Remón A, Tresserra-Rimbau A, Pons A, Tur JA, Martorell M, Ros E, et al. Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial. Nutr Metab Cardiovasc Dis. 2015;25:60–7.
Gurău F, Baldoni S, Prattichizzo F, Espinosa E, Amenta F, Procopio AD, et al. Anti-senescence compounds: A potential nutraceutical approach to healthy aging. Ageing Res Rev. 2018;46:14–31.
Hickson LJ, Langhi Prata LGP, Bobart SA, Evans TK, Giorgadze N, Hashmi SK, et al. Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of Dasatinib plus Quercetin in individuals with diabetic kidney disease. EBioMedicine. 2019;47:446–56.
Del Bo’ C, Marino M, Martini D, Tucci M, Ciappellano S, Riso P, et al. Overview of human intervention studies evaluating the impact of the Mediterranean diet on markers of DNA damage. Nutrients. 2019;11. https://doi.org/10.3390/nu11020391.
Corina A, Rangel-Zúñiga OA, Jiménez-Lucena R, Alcalá-Díaz JF, Quintana-Navarro G, Yubero-Serrano EM, et al. Low intake of vitamin E accelerates cellular aging in patients with established cardiovascular disease: The CORDIOPREV study. J Gerontol Ser A. 2019;74:770–7.
Durani LW, Jaafar F, Tan JK, Tajul Arifin K, Mohd Yusof YA, Wan Ngah WZ, et al. Targeting genes in insulin-associated signalling pathway, DNA damage, cell proliferation and cell differentiation pathways by tocotrienol-rich fraction in preventing cellular senescence of human diploid fibroblasts. Clin Ter. 2015;166:e365–73.
López-Uriarte P, Nogués R, Saez G, Bulló M, Romeu M, Masana L, et al. Effect of nut consumption on oxidative stress and the endothelial function in metabolic syndrome. Clin Nutr. 2010;29:373–80.
Riso P, Martini D, Visioli F, Martinetti A, Porrini M. Effect of broccoli intake on markers related to oxidative stress and cancer risk in healthy smokers and nonsmokers. Nutr Cancer. 2009;61:232–7.
Moser B, Szekeres T, Bieglmayer C, Wagner K-H, Mišík M, Kundi M, et al. Impact of spinach consumption on DNA stability in peripheral lymphocytes and on biochemical blood parameters: results of a human intervention trial. Eur J Nutr. 2011;50:587–94.
Mihaylova MM, Sabatini DM, Yilmaz ÖH. Dietary and metabolic control of stem cell function in physiology and cancer. Cell Stem Cell. 2014;14:292–305.
Gruver A, Hudson L, Sempowski G. Immunosenescence of ageing. J Pathol. 2007;211:144–56.
Fulop T, Larbi A, Dupuis G, Le Page A, Frost EH, Cohen AA, et al. Immunosenescence and inflamm-aging as two sides of the same coin: friends or foes? Front Immunol. 2018;8:1960.
Ungvari Z, Kaley G, de Cabo R, Sonntag WE, Csiszar A. Mechanisms of vascular aging: new perspectives. J Gerontol A Biol Sci Med Sci. 2010;65:1028–41.
Marin C, Delgado-Lista J, Ramirez R, Carracedo J, Caballero J, Perez-Martinez P, et al. Mediterranean diet reduces senescence-associated stress in endothelial cells. AGE. 2012;34:1309–16.
Cesari F, Marcucci R, Gori AM, Burgisser C, Francini S, Roberts AT, et al. Adherence to lifestyle modifications after a cardiac rehabilitation program and endothelial progenitor cells. A six-month follow-up study. Thromb Haemost. 2014;112:196–204.
Cesari F, Sofi F, Molino Lova R, Vannetti F, Pasquini G, Cecchi F, et al. Aging process, adherence to Mediterranean diet and nutritional status in a large cohort of nonagenarians: effects on endothelial progenitor cells. Nutr Metab Cardiovasc Dis. 2018;28:84–90.
Marin C, Ramirez R, Delgado-Lista J, Yubero-Serrano EM, Perez-Martinez P, Carracedo J, et al. Mediterranean diet reduces endothelial damage and improves the regenerative capacity of endothelium. Am J Clin Nutr. 2011;93:267–74.
Fernández JM, Rosado-Álvarez D, Da Silva Grigoletto ME, Rangel-Zúñiga OA, Landaeta-Díaz LL, Caballero-Villarraso J, et al. Moderate-to-high-intensity training and a hypocaloric Mediterranean diet enhance endothelial progenitor cells and fitness in subjects with the metabolic syndrome. Clin Sci. 2012;123:361–73.
Shannon OM, Mendes I, Köchl C, Mazidi M, Ashor AW, Rubele S, et al. Mediterranean diet increases endothelial function in adults: a systematic review and meta-analysis of randomized controlled trials. J Nutr. 2020;150:1151–9.
Liu H, Huang H, Li B, Wu D, Wang F, Zheng Xhua, et al. Olive oil in the prevention and treatment of osteoporosis after artificial menopause. Clin Interv Aging. 2014;9:2087–95.
Fernández-Real JM, Bulló M, Moreno-Navarrete JM, Ricart W, Ros E, Estruch R, et al. A Mediterranean diet enriched with olive oil is associated with higher serum total osteocalcin levels in elderly men at high cardiovascular risk. J Clin Endocrinol Metab. 2012;97:3792–8.
Mittelbrunn M, Sánchez-Madrid F. Intercellular communication: diverse structures for exchange of genetic information. Nat Rev Mol Cell Biol. 2012;13:328–35.
Leone A, Longo C, Trosko JE. The chemopreventive role of dietary phytochemicals through gap junctional intercellular communication. Phytochem Rev. 2012;11:285–307.
Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.
Cohen HJ, Pieper CF, Harris T, Rao KM, Currie MS. The association of plasma IL-6 levels with functional disability in community-dwelling elderly. J Gerontol A Biol Sci Med Sci. 1997;52:M201–8.
Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69:S4–9.
Rosano C, Marsland AL, Gianaros PJ. Maintaining brain health by monitoring inflammatory processes: a mechanism to promote successful aging. Aging Dis. 2012;3:16–33.
Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger WH, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106:506–12.
Michaud M, Balardy L, Moulis G, Gaudin C, Peyrot C, Vellas B, et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14:877–82.
Szarc vel SzicK, Declerck K, Vidakovi M, Vanden Berghe W. From inflammaging to healthy aging by dietary lifestyle choices: is epigenetics the key to personalized nutrition? Clin Epigenetics. 2015;7:33.
Xia S, Zhang X, Zheng S, Khanabdali R, Kalionis B, Wu J, et al. An update on inflamm-aging: mechanisms, prevention, and treatment. J Immunol Res. 2016;2016:8426874.
Fransen F, van Beek AA, Borghuis T, Aidy SE, Hugenholtz F, van der Gaast-de C, et al. Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice. Front Immunol. 2017;8:1385.
Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006;145:1–11.
Mena M-P, Sacanella E, Vazquez-Agell M, Morales M, Fitó M, Escoda R, et al. Inhibition of circulating immune cell activation: a molecular antiinflammatory effect of the Mediterranean diet. Am J Clin Nutr. 2009;89:248–56.
Casas R, Sacanella E, Urpí-Sardà M, Chiva-Blanch G, Ros E, Martínez-González M-A, et al. The effects of the Mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease. A randomized trial. PloS ONE. 2014;9:e100084.
Salas-Salvadó J, Garcia-Arellano A, Estruch R, Marquez-Sandoval F, Corella D, Fiol M, et al. Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. Eur J Clin Nutr. 2008;62:651–9.
Richard C, Royer M-M, Couture P, Cianflone K, Rezvani R, Desroches S, et al. Effect of the Mediterranean diet on plasma adipokine concentrations in men with metabolic syndrome. Metabolism. 2013;62:1803–10.
Sureda A, Bibiloni MDM, Julibert A, Bouzas C, Argelich E, Llompart I, et al. Adherence to the Mediterranean diet and inflammatory markers. Nutrients. 2018;10:62.
Perez-Martinez P, Lopez-Miranda J, Blanco-Colio L, Bellido C, Jimenez Y, Moreno JA, et al. The chronic intake of a Mediterranean diet enriched in virgin olive oil, decreases nuclear transcription factor kappaB activation in peripheral blood mononuclear cells from healthy men. Atherosclerosis. 2007;194:e141–6.
Park Y-M, Zhang J, Steck SE, Fung TT, Hazlett LJ, Han K, et al. Obesity mediates the association between Mediterranean diet consumption and insulin resistance and inflammation in US adults. J Nutr. 2017;147:563–71.
Ordovas JM, Ferguson LR, Tai ES, Mathers JC. Personalised nutrition and health. BMJ. 2018;361:k2173.
This research was supported by the Alzheimer’s Research UK Prevention and Risk Reduction Fund (ARUK-PRRF2017-006) and the UK Nutrition Research Partnership (UK NRP), an initiative supported by the Medical Research Council (MRC), Biotechnology and Biological Sciences Research Council (BBSRC) and the National Institute for Health Research (NIHR) (MR/T001852/1).
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Shannon, O.M., Ashor, A.W., Scialo, F. et al. Mediterranean diet and the hallmarks of ageing. Eur J Clin Nutr 75, 1176–1192 (2021). https://doi.org/10.1038/s41430-020-00841-x
This article is cited by
Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review
Food Science and Biotechnology (2022)
Dietary nitrate and population health: a narrative review of the translational potential of existing laboratory studies
BMC Sports Science, Medicine and Rehabilitation (2021)
The journal of nutrition, health & aging (2021)