Abstract
BACKGROUND: Recent studies have suggested that gestational diabetes mellitus (GDM) can accelerate cellular aging in multiple cell types in offspring, but its impact on immune senescence remains uncertain. Our prior study reveals GDM increased the secretion of inflammatory factors by monocytes in offspring. This study discovered the transcriptome characteristics of aging monocytes at the single-cell level and explore the impact of GDM on the progression of monocyte aging in offspring. METHOD: Single-cell sequencing data from 56 healthy individuals (aged 0-100 years), comprising self-measured samples (n = 6) and publicly available datasets from the Gene Expression Omnibus (GEO, n = 50), were analyzed to characterize monocyte senescence. Linear mixed-effects modeling was used to screen for age-related genes. A random forest model was created to predict immune age in monocytes, allowing for quantitative assessment of aging. RESULTS: We detected an increase in the number of inflammatory monocytes expressing IL1B and CXCL8 with age. Two age-related gene expression patterns were identified in monocytes. Analysis of offspring monocytes from mothers with GDM suggested that exposure to a GDM environment in the womb may lead to increased expression of aging-related genes, a hindered cell cycle, and increased immune age. The immune age of monocytes at birth is significantly linked to maternal weight gain, high fasting blood glucose levels, and cord blood C-peptide levels during pregnancy. CONCLUSIONS: Exposure to GDM during pregnancy accelerates aging in offspring immune cells. Monitoring maternal weight and blood sugar during GDM can help prevent negative effects on the offspring immune system.