Telemore length in different Spanish age groupassociation with diet, genetics and adiposity traits

Resumen

Telomere length (TL) has been proposed as a biomarker of biological aging processes because telomeres shorten within each cell division. But the fact that TL varies considerably among individuals of the same chronological age implies the need to investigate potential lifestyle and genetic aspects that influence TL. In addition, TL has also been considered a general risk factor for age-related chronic diseases, such as cancer, type 2 diabetes or cardiovascular disease. Since obesity and shortened telomeres are associated with the increased risk of metabolic disorders, we wondered whether TL may be longitudinally related to adiposity. In Chapter 1, we found that higher dietary TAC intake and lower white bread consumption were associated with longer telomeres in children and adolescents from the GENOI study. In Chapter 2, high cardiovascular risk individuals carrying the Pro12Ala polymorphism of the PPARγ2 gene displayed a lower rate of telomere shortening after a 5-year nutritional intervention in the frame of the PREDIMED-NAVARRA trial. Furthermore, a potent gene-diet interaction was observed since a higher adherence to a Mediterranean dietary pattern strengthens the prevention of telomere shortening among Ala carriers. In Chapter 3, a 2-month intensive weight loss treatment led to an increased leukocyte TL in obese adolescents from the EVASYON study. Besides, higher baseline TL predicted a better weight loss response after the 2-month intensive period and also after a 6-month follow-up period, but only among boys, suggesting a modification effect by sex at puberty. In Chapter 4, a decrease in obesity risk was linked to an increased TL after 5 years of a nutritional intervention in subjects participating in the PREDIMED-NAVARRA trial. Moreover, those subjects presenting longer telomeres at baseline reported a better improvement of obesity traits after the 5-year period of dietary intervention. In summary, the results presented in this thesis have suggested a potential role of an antioxidant rich diet as well as of the gene variant Pro12Ala in maintaining TL. Moreover, an inverse longitudinal relationship between TL and changes in adiposity in two different age groups, high cardiovascular risk adults and obese adolescents, was observed after lifestyle interventions. Notably, a higher baseline TL was associated with a better improvement in anthropometric parameters, proposing TL as a biomarker of adiposity. Further research is necessary to better understand TL homeostasis in metabolic diseases, and to identify potential factors that could modulate age-dependent telomere erosion.