Coltell Oscar, Asensio Eva M, Sorlí José V, Ortega-Azorín Carolina, Fernández-Carrión Rebeca, Pascual Eva C, Barragán Rocío, González José I, Estruch Ramon, Alzate Juan F, Pérez-Fidalgo Alejandro, Portolés Olga, Ordovas Jose M, Corella Dolores
Department of Computer Languages and Systems, Universitat Jaume I, 12071 Castellón, Spain.
CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain.
Antioxidants (Basel). 2023 Nov 15;12(11):2004. doi: 10.3390/antiox12112004.
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 ( < 0.05) between DNAmTL and candidate genes (, , , and ), 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; = 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; = 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 ( < 1 × 10) for DNAmTL (intergenics, in the , , and 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.
生物衰老 是慢性疾病的一个相关风险因素，人们已经提出了几个用于衡量该因素的指标，其中端粒长度（TL）是研究最多的指标之一。氧化应激可能会调节端粒缩短，而端粒缩短与风险增加有关。我们使用一种新的端粒长度估计方法，研究了坚持地中海饮食（MedDiet）这种富含抗氧化剂的饮食模式是否与更长的端粒长度相关。我们使用DNA甲基化算法（DNAmTL）测定了414名来自西班牙的心血管疾病高风险受试者的端粒长度。通过一个经过验证的评分来评估对地中海饮食的坚持程度，并分析了候选基因和全基因组水平上的基因变异。我们观察到DNAmTL与候选基因（、、和）之间存在几个显著关联（<0.05），这有助于证明DNAmTL作为该人群生物标志物的有效性。在整个样本中，对地中海饮食的更高坚持程度与端粒较短的较低几率相关（OR = 0.93；95%置信区间：0.85 - 0.99；完全多变量调整后 = 0.049）。然而，这种关联在女性中比在男性中更强。同样，在女性中，我们观察到作为连续变量的地中海饮食评分与DNAmTL之间存在直接关联（β = 0.015；标准误：0.005； = 0.003），这表明坚持程度每增加一分与端粒长度平均增加0.015±0.005 kb相关。在检查总体评分中的特定饮食项目时，我们发现水果、鱼类、“sofrito”和全谷物在女性中表现出最强的关联。结合这些项目的新评分在整个人群中具有显著相关性。在全基因组关联研究（GWAS）中，我们在DNAmTL的提示性显著水平（<1×10）上鉴定出10个多态性（基因间区域，在、和基因中），并检测到一些基因 - 地中海饮食对DNAmTL的调节作用。由于这是第一项分析DNAmTL估计方法、遗传学以及地中海饮食调节作用的研究，需要更多研究来证实这些发现。
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