Assessing the Causal Association between Biological Aging Biomarkers and the Development of Cerebral Small Vessel Disease: A Mendelian Randomization Study

• Published in: Biology (Basel, Switzerland) Vol. 12; no. 5; p. 660
• Main Authors: Lin, Biying, Mu, Yuzhu, Ding, Zhongxiang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27.04.2023; MDPI
• Subjects: Age; Aging; biological aging; Biological markers; Biomarkers; Blood pressure; cerebral small vessel disease; Cerebrovascular diseases; Cohort analysis; Communication; Diabetes; Disease; DNA methylation; epigenetic clock; Epigenetic inheritance; Epigenetics; Genomes; Genomics; Hypertension; leukocyte telomere length; Medical research; Medicine, Experimental; Medicine, Preventive; Mendelian randomization; Meta-analysis; Methods; Preventive health services; Risk factors; Sensitivity analysis; Telomeres; Vascular diseases; biological aging; cerebral small vessel disease; Mendelian randomization; leukocyte telomere length; epigenetic clock
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12050660

Biological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers in the development of CSVD. We performed a Mendelian randomization (MR) study of LTL and four epigenetic clocks on ten subclinical and clinical CSVD measures. We obtained genome-wide association (GWAS) data for LTL from the UK Biobank (N = 472,174). Data on epigenetic clocks were derived from a meta-analysis (N = 34,710), and CSVD data (N cases =1293-18,381; N controls = 25,806-105,974) were extracted from the Cerebrovascular Disease Knowledge Portal. We found that genetically determined LTL and epigenetic clocks were not individually associated with ten measures of CSVD (IVW > 0.05), and this result was consistent across sensitivity analyses. Our findings imply that LTL and epigenetic clocks may not help in predicting CSVD development as causal prognostic biomarkers. Further studies are needed to illustrate the potential of reverse biological aging in serving as an effective form of preventive therapy for CSVD.