• Zhenxian Jia, Feng Qiu, Yujie He, Huan Chen, Chenhui Yang, Hongxiu Liu, Tongzhang Zheng, Shunqing Xu, Shiqiong Wang, and Yuanyuan Li.
• Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, Hubei, 430030, China.
• Bmc Med. 2024 Oct 8; 22 (1): 429429.

BackgroundTelomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old.MethodsThis research involved 895 mother-child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath's epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones.ResultsThe linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), - 13.22 (- 23.21 to - 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), - 14.13 (- 21.59 to - 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than - 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than - 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than - 1.35, followed by a plateau between - 1.35 and - 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than - 0.67.ConclusionsIn this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.© 2024. The Author(s).

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