Non-linear age-related change in human Interleukin-11 and the receptor subunit alpha DNA methylation

Interleukin-11 (IL-11) is a cytokine involved in inflammatory processes and a previous study showed that blocking or knocking down IL11 in mice prolongs a healthy lifespan. This study investigates DNA methylation (DNAm) changes in the IL11 and IL-11 receptor subunit alpha (IL-11RA) gene across ages to explore age-related epigenetic patterns that may influence IL-11 production and pathway sensitivity.

A genome-wide DNAm database focusing on Cytosine-phosphate-Guanine (CpG) sites within the IL11 and IL11RA was analyzed. Hierarchical regression analyses examined the relationship between DNAm, age, and the squared age term for quadratic associations.

The database comprised 10,297 samples (5156 males and 5141 females) with a mean age of 53.9 years (SD = 14.1 years). The majority of IL11 and IL11RA CpG sites in the TSS1500 and 3'UTR regions exhibited significant inverse U-shaped associations with age. DNAm levels were low during youth, increased in middle age (40s-50s), and decreased again in older age.

The observed inverse U-shaped DNAm patterns in the IL11 and IL11RA suggest non-linear age-related regulation that may influence IL-11 expression and sensitivity. These findings indicate that IL-11 may have different roles across life stages and suggest that therapeutic interventions targeting IL-11 should consider age-specific effects.