Analyzing the causal role of blood cells in aging: a Mendelian randomization study.

Jingjing Zhang, Xin Zhang, Boan Xiao, Jiecai Ouyang, Peng Wang, Xiaobin Peng

The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China.The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China. · pubmed

Paper

Abstract

Blood cells are crucial components of the human body, closely linked to the aging process. This study aims to explore the causal relationship between 91 blood cell phenotypes and aging through Mendelian randomization (MR) analysis. Exposure data from genome-wide association studies (GWAS) was extracted from the GWAS of blood cell perturbation phenotypes in 2,600 European individuals. Initial analysis utilized GWAS data related to aging from the GWAS Catalog database GCST90014288, with inverse-variance weighting as the primary method for causal analysis. Sensitivity analyses included Cochran's Q test, MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. For significant associations, replication and meta-analysis were conducted using independent aging GWAS data from GCST90014300. Initial analysis revealed that environmental peroxide-impacted red blood cells and ciprofloxacin-impacted reticulocytes accelerated aging. Additionally, elevated neutrophil levels were found to accelerate aging, while LiCl-impacted neutrophils reduced aging risk. Replication and meta-analysis showed consistent results: ciprofloxacin-impacted reticulocytes and elevated neutrophil levels increased the risk of aging, while LiCl-impacted neutrophils reduced the risk. RBCs showed no significant impact on aging progression. Sensitivity analyses confirmed the robustness and reliability of these positive findings. Our study provides evidence of a causal relationship between three blood cell disturbance phenotypes and human aging.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper investigates the causal relationship between blood cell phenotypes and aging, which aligns with the exploration of root causes of aging. However, while the findings are interesting, they primarily contribute incremental knowledge rather than groundbreaking insights. The study's focus on specific blood cell disturbances and their association with aging does not significantly advance the broader understanding of aging mechanisms or lifespan extension.

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