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

IF 4.4 4区医学 Q1 GERIATRICS & GERONTOLOGY

Biogerontology Pub Date : 2024-11-04 DOI:10.1007/s10522-024-10148-0

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

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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.

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分析血细胞在衰老中的因果作用：孟德尔随机研究。

血细胞是人体的重要组成部分，与衰老过程密切相关。本研究旨在通过孟德尔随机化（MR）分析探讨 91 种血细胞表型与衰老之间的因果关系。全基因组关联研究（GWAS）的暴露数据是从 2,600 名欧洲人的血细胞扰乱表型 GWAS 中提取的。初步分析利用了 GWAS 目录数据库 GCST90014288 中与衰老有关的 GWAS 数据，并将反方差加权作为因果分析的主要方法。敏感性分析包括 Cochran's Q 检验、MR-Egger 截距检验、MR-PRESSO 和撇除分析。对于重要的关联，则使用来自 GCST90014300 的独立老龄化 GWAS 数据进行了复制和荟萃分析。初步分析表明，受环境过氧化物影响的红细胞和受环丙沙星影响的网状细胞会加速衰老。此外，还发现中性粒细胞水平升高会加速衰老，而受氯化锂影响的中性粒细胞则会降低衰老风险。复制和荟萃分析显示出一致的结果：环丙沙星影响的网织红细胞和中性粒细胞水平升高会增加衰老风险，而锂盐影响的中性粒细胞会降低衰老风险。红细胞对衰老进程没有明显影响。敏感性分析证实了这些积极发现的稳健性和可靠性。我们的研究为三种血细胞紊乱表型与人类衰老之间的因果关系提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biogerontology 医学-老年医学

CiteScore

8.00

自引率

4.40%

发文量

审稿时长

>12 weeks

期刊介绍： The journal Biogerontology offers a platform for research which aims primarily at achieving healthy old age accompanied by improved longevity. The focus is on efforts to understand, prevent, cure or minimize age-related impairments. Biogerontology provides a peer-reviewed forum for publishing original research data, new ideas and discussions on modulating the aging process by physical, chemical and biological means, including transgenic and knockout organisms; cell culture systems to develop new approaches and health care products for maintaining or recovering the lost biochemical functions; immunology, autoimmunity and infection in aging; vertebrates, invertebrates, micro-organisms and plants for experimental studies on genetic determinants of aging and longevity; biodemography and theoretical models linking aging and survival kinetics.