Genetic variation and environmental factors in biological and arterial ageing.

ABSTRACT

Arterial ageing is a complex continuously distributed phenotype, which comes about through the interaction between inherited susceptibility, life-style and environmental factors. We used an integrated approach combining methods from genetics, molecular biology and population sciences to study the role of genetic variation and environmental factors in biological ageing. The discussed work comprises four population based studies of which two had a prospective design and two integrated recently developed biomolecular markers of ageing with classical epidemiological tools. The striking variability in the age of the manifestation of cardiovascular diseases is not fully explained by conventional risk factors. Variation in biological age has been suggested. The initial telomere length of a person is mainly determined by genetic factors. In this regard, we noticed robust correlations in telomere length between fathers and daughters, between mothers and both sons and daughters, and among siblings. X-linked inheritance of telomere length is the most likely explanation for these findings. Telomere length shortens with each cell division, and exposition to harmful environmental factors results in shorter telomere length as we observed in smokers. Telomere length correlated with the distensibility of the carotid artery and oxidative stress and inflammation are major determinants of arterial and biological ageing. In this context, selenium a component of antioxidant enzymes such as glutathione peroxidase, correlated inversely with blood pressure in the population at large. Oxidative stress and inflammation are major determinants of arterial and biological ageing. If telomeres are indeed causally involved in the pathogenesis of arterial ageing, this might provide new avenues for future preventive and therapeutic strategies.