Investigating the impact of metabolic syndrome traits on telomere length: a Mendelian randomization study

ObjectiveObservational studies have reported bidirectional associations between metabolic syndrome (MetS) traits and short leukocyte telomere length (LTL), a TL marker in somatic tissues and a proposed risk factor for age-related degenerative diseases. However, in Mendelian randomization studies, longer LTL has been paradoxically associated with higher MetS risk. This study investigated the hypothesis that shorter LTL might be a consequence of metabolic dysfunction. MethodsThis study undertook univariable and multivariable Mendelian randomization. As instrumental variables for MetS traits, all of the genome-wide significant independent signals identified in genome-wide association studies for anthropometric, glycemic, lipid, and blood pressure traits conducted in European individuals were used. Summary-level data for LTL were obtained from a genome-wide association study conducted in the UK Biobank. ResultsHigher BMI was associated with shorter LTL (& beta; = -0.039, 95% CI: -0.058 to -0.020, p = 5 x 10(-5)) equivalent to 1.70 years of age-related LTL change. In contrast, higher low-density lipoprotein cholesterol was associated with longer LTL (& beta; = 0.022, 95% CI: 0.007 to 0.037, p = 0.003) equivalent to 0.96 years of age-related LTL change. Mechanistically, increased low-grade systemic inflammation, as measured by circulating C-reactive protein, and lower circulating linoleic acid levels might link higher BMI to shorter LTL. ConclusionsOverweight and obesity might promote the development of aging-related degenerative diseases by accelerating telomere shortening.