The causal relationship between blood cell traits and aging: a Mendelian randomization study

• Published in: BMC geriatrics Vol. 25; no. 1; pp. 393 - 14
• Main Authors: Chen, Peng, Zhou, Yi-Hang, Wei, Xin, Wei, Hua-Gui, Li, Bo, Ou-Yang, Ling
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.05.2025; BioMed Central; BMC
• Subjects: 25-Hydroxyvitamin D; Aged; Aging; Aging - blood; Aging - genetics; Blood; Blood cell; Blood Cells - metabolism; C-reactive protein; Cholesterol; DNA methylation; Epigenetic clock; Epigenetics; Female; Frailty; Frailty - blood; Frailty - genetics; Frailty index; Genomes; Health aspects; Health care; Humans; Leukocytes (eosinophilic); Life expectancy; Lymphocytes; Male; Medical examination; Mendelian randomization; Mendelian Randomization Analysis - methods; Metabolites; Middle Aged; Mortality; Physiological aspects; Population studies; Public health; Statistics; Telomere length; Telomeres; China; Aging; Blood cell; Frailty index; Epigenetic clock; Mendelian randomization; Telomere length
• ISSN: 1471-2318; 1471-2318
• DOI: 10.1186/s12877-025-06051-z

The global population is aging rapidly, raising significant concerns about public health issues. Routine blood tests, which assess blood cell traits, are commonly performed clinical laboratory tests. Understanding the intricate relationship between blood cell traits and aging is vital for identifying individuals at risk of early decline in health. This study employed bidirectional Mendelian randomization (MR) to explore causal links between 36 blood cell traits and aging indicators, including frailty index (FI), telomere length (TL), and epigenetic aging clocks. Univariate MR analysis primarily used inverse variance weighted, MR-Egger, weighted median, and weighted mode methods. Multivariate MR was applied to investigate independent effects of each blood cell trait on aging utilizing multivariable inverse variance-weighted techniques. Furthermore, the mediating effects of nine potential mediators, such as 25-hydroxyvitamin D, C-reactive protein, and cholesterol levels on the causal relationship between blood cell traits and aging were examined by a mediation analysis. The study revealed significant causal associations: eosinophil counts were positively associated with FI (odds ratio (OR) = 1.063, p = 1.4e-07). Mean corpuscular volume (MCV) was linked to telomere length (OR = 0.978, p = 0.0001). Lymphocyte counts showed causal connections with epigenetic aging clocks (GrimAge acceleration: OR = 0.614, p = 7.0e-08; Hannum age acceleration: OR = 0.519, p = 5.4e-11; and PhenoAge acceleration: OR = 0.519, p = 5.4e-11). This MR study uncovered significant causal relationships between blood cell traits such as eosinophil counts, MCV, and lymphocyte counts, with aging indicators. Monitoring these traits in routine blood tests can provide valuable insights for assessing age-related health risks and promoting healthy aging.