探讨代谢综合征特征对端粒长度的影响：一项孟德尔随机化研究。

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

机构信息

Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.

Section on Clinical Genomics and Experimental Therapeutics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Obesity (Silver Spring). 2023 Aug;31(8):2189-2198. doi: 10.1002/oby.23810. Epub 2023 Jul 6.

DOI:10.1002/oby.23810

PMID:37415075

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10658743/

Abstract

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 ) 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.

摘要

目的

观察性研究报告代谢综合征（MetS）特征与短白细胞端粒长度（LTL）之间存在双向关联，LTL 是体细胞组织中的 TL 标志物，也是与年龄相关退行性疾病风险相关的一个提议的危险因素。然而，在孟德尔随机化研究中，较长的 LTL 与更高的 MetS 风险呈反常相关。本研究旨在检验以下假说，即较短的 LTL 可能是代谢功能障碍的结果。

方法

本研究进行了单变量和多变量孟德尔随机化分析。作为 MetS 特征的工具变量，本研究使用了在欧洲人群中进行的全基因组关联研究中确定的所有与体重指数、血糖、血脂和血压特征相关的全基因组显著独立信号。LTL 的汇总水平数据来自在英国生物银行进行的全基因组关联研究。

结果

较高的体重指数与较短的 LTL 相关（β=−0.039，95%CI：−0.058 至−0.020，p=5×10），相当于与年龄相关的 LTL 变化 1.70 年。相比之下，较高的低密度脂蛋白胆固醇与较长的 LTL 相关（β=0.022，95%CI：0.007 至 0.037，p=0.003），相当于与年龄相关的 LTL 变化 0.96 年。从机制上讲，循环 C 反应蛋白测量的低度全身性炎症增加和循环亚油酸水平降低可能将较高的体重指数与较短的 LTL 联系起来。