Research Paper Volume 16, Issue 8 pp 7387—7404
New insights from bidirectional Mendelian randomization: causal relationships between telomere length and mitochondrial DNA copy number in aging biomarkers
- 1 Zhongshan City People’s Hospital, Xinxiang Medical University, Xinxiang 453003, Henan, China
- 2 Department of Radiation Oncology, Zhongshan City People’s Hospital, Zhongshan 528403, Guangdong, China
- 3 Department of Radiation Oncology, Jiangmen Central Hospital, Jiangmen 529000, Guangdong, China
Received: January 8, 2024 Accepted: March 28, 2024 Published: April 24, 2024
https://doi.org/10.18632/aging.205765How to Cite
Copyright: © 2024 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Mitochondrial DNA (mtDNA) copy number and telomere length (TL) are dynamic factors that have been linked to the aging process in organisms. However, the causal relationship between these variables remains uncertain. In this research, instrumental variables (IVs) related to mtDNA copy number and TL were obtained from publicly available genome-wide association studies (GWAS). Through bidirectional Mendelian randomization (MR) analysis, we examined the potential causal relationship between these factors. The forward analysis, with mtDNA copy number as the exposure and TL as the outcome, did not reveal a significant effect (B=-0.004, P>0.05). On the contrary, upon conducting a reverse analysis, it was found that there exists a positive causal relationship (B=0.054, P<0.05). Sensitivity analyses further confirmed the reliability of these results. The outcomes of this study indicate a one-way positive causal relationship, indicating that telomere shortening in the aging process may lead to a decrease in mtDNA copy number, providing new perspectives on their biological mechanisms.
Abbreviations
MR: mendelian randomization; mtDNA: mitochondrial DNA; TL: telomere length; IVs: instrumental variables; GWAS: genome-wide association studies; IVW: inverse variance weighted mre; MRE: random-effects model; ROS: reactive oxygen species; SNP: single nucleotide polymorphism..