Constantinos Christodoulides

Objective Observational 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. Methods This 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. Results Higher BMI was associated with shorter LTL ( β = −0.039, 95% CI: −0.058 to −0.020, p = 5 × 10 −5 ) equivalent to 1.70 years of age‐related LTL change. In contrast, higher low‐density lipoprotein cholesterol was associated with longer LTL ( β = 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. Conclusions Overweight and obesity might promote the development of aging‐related degenerative diseases by accelerating telomere shortening.