Associations between the new DNA-methylation-based telo-mere length estimator, the Mediterranean diet, and genetics in a Spanish population at high cardiovascular risk

Authors: COLTELL, OSCAR - University Of Jaume; ASENSIO, EVA - University Of Valencia; SORLI, JOSE - Instituto De Salud Carlos Iii; ORTEGA-AZORIN, CAROLINA - Instituto De Salud Carlos Iii; FERNANDEZ-CARRION, REBECA - Instituto De Salud Carlos Iii; PASCUAL, EVA - University Of Valencia; BARRAGAN, ROCIO - Instituto De Salud Carlos Iii; GONZALEZ, JOSE - Instituto De Salud Carlos Iii; ESTRUCH, RAMON - University Of Barcelona; ALZATE, JUAN - University Of Antioquia; PEREZ FIDALGO, ALEJANDRO - University Clinical Hospital Of Valencia; PORTOLES, OLGA - University Of Valencia; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Antioxidants
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/14/2023
Publication Date: 11/15/2023
Citation: Coltell, O., Asensio, E.M., Sorli, J.V., Ortega-Azorin, C., Fernandez-Carrion, R., Pascual, E.C., Barragan, R., Gonzalez, J.I., Estruch, R., Alzate, J.F., Perez-Fidalgo, A., Portoles, O., Ordovas, J.M. 2023. Associations between the new DNA-methylation-based telo-mere length estimator, the Mediterranean diet, and genetics in a Spanish population at high cardiovascular risk. Antioxidants. https://doi.org/10.3390/antiox12112004.
DOI: https://doi.org/10.3390/antiox12112004

Interpretive Summary: We studied how following a Mediterranean diet, which is rich in antioxidants, might affect aging. We used a new method to measure aging by looking at specific regions of DNA called telomeres in 414 people in Spain who were at risk for heart problems. People who stuck closely to the Mediterranean diet tended to have better aging markers. This was especially true for women. Certain foods like fruits, fish, and whole grains were particularly beneficial. Additionally, the study looked at how specific genetic factors might interact with the diet in affecting these aging markers. While these findings are new and need more research, they suggest that what you eat can influence how your body ages.

Technical Abstract: Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high-cardiovascular risk from Spain. Adherence to MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations (p<0.05) between DNAmTL and candidate genes (TERT, TERF2, RTEL1, and DCAF4), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR=0.93; 95% CI: 0.85-0.99; p=0.049, after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta=0.015; SE: 0.005; p=0.003), indicating that a one-point increase in the adherence was related to an average increase of 0.015+\-0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, "sofrito," and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the GWAS analysis, we identified ten SNPs at the suggestive level of significance (p<1x10-5) for DNAmTL (intergenics, in the IQSEC1, NCAPG2, and ABI3BP genes) and detected some gene-MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings.