Non-linear Age-related Change in Human Interleukin-11 and the receptor subunit alpha DNA Methylation
Abstract
Introduction
Interleukin-11 (IL-11) is a cytokine involved in inflammatory processes and a previous study showed that blocking or knocking downIL11in mice prolongs a healthy lifespan. This study investigates DNA methylation (DNAm) changes in theIL11and IL-11 receptor subunit alpha (IL-11RA) gene across ages to reveal how aging might influence IL-11 production and sensitivity.
Methods
A genome-wide DNAm database focusing on Cytosine-phosphate-Guanine (CpG) sites within theIL11andIL11RAwas analyzed. Hierarchical regression analyses examined the relationship between DNAm, age, and the squared age term for quadratic associations.
Results
The database comprised 10,297 samples (5,156 males and 5,141 females) with a mean age of 53.9 years (SD = 14.1 years). The majority ofIL11andIL11RACpG 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.
Conclusion
The observed inverse U-shaped DNAm patterns in theIL11andIL11RAsuggest n non-linear, age-related regulation of 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.
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