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

Authors: COLTELL, OSCAR - Jaume I University; ASENSIO, EVA - Valencia University; 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 - Valencia University; 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 - Valencia University; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; CORELLA, DOLORES - Valencia 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., Corella, D. 2023. Associations between the new DNA-methylation-based telomere 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: Scientists examined how eating a Mediterranean diet, which is full of foods that help fight off disease, might keep our body's cells young, especially in people at risk for heart problems. They used a new way to measure cell age by looking at DNA. People who followed this healthy diet closely had younger-looking cells, and this effect was even more pronounced in women. The study suggests that eating lots of fruits, fish, and whole grains could help keep our cells youthful. More research is needed, but it's a clue that what we eat might help us stay healthy longer.

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 the 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 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 genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance (p < 1x 10-5) 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.