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Introduction COPD is now recognised as a disease of multifactorial aetiology, with low lung function trajectory (LLFT) in early life a major risk factor. Accelerated aging and cellular senescence may be important to COPD pathogenesis. Epigenetic age acceleration (EAA) and senescence-associated plasma proteins are associated with lower adult lung function and COPD, but little is known of how they relate to high-risk early-life LLFT.Aim To investigate whether childhood EAA and plasma concentrations of senescence-associated proteins are associated with subsequent LLFT into young adulthood.Methods Lung function was measured at ages 8, 15, 24 and 30 years in the Avon Longitudinal Study of Parents and Children. Latent profile analysis was used to derive FEV 1 trajectory groups from participants with ≥2 measurements (n=5,232;% predicted for age, sex and height). The final model was selected based on goodness-of-fit and adequate group size.DNA methylation was quantified at age 7 or 9 (n=1,144) using the Illumina 450 k array. EAA was estimated by five different approaches: Horvath intrinsic EAA (IEAA), Hannum extrinsic EAA (EEAA), DNAm PhenoAge, DNAm GrimAge and DamAge EAA.Proteomics were assayed from blood plasma at age 9 (n=2,961) using the O-link Target 96 inflammation panel, with 13 senescence-associated proteins analysed as exposures.Logistic regression provided the odds ratio of LLFT per year of EAA, or log2 increase in plasma protein concentration, after adjusting for sex and age at blood sampling.Results Five parallel trajectories were identified, with persistently low (n=158; mean FEV1=72.6%) and below average (n=1423; mean FEV1=87.7%) modelled as LLFT and compared to average and above. We did not find evidence of an association between EAA and subsequent LLFT. FDR adjusted associations (p<0.10) with persistently low trajectory were evident for plasma concentrations of CXCL10 (OR per quintile 1.26 [1.04–1.52]), IL6 (OR per log 2 rise 1.43 [1.06–1.91]) and IL33 (OR per log2 rise 1.93 [1.19–3.14]) (figure 1).Abstract S117 Figure 1Odds ratios for persistently low trajectory by EAA and plasma protein concentrationConclusions Childhood EAA was not associated with subsequent LLFT in our sample. Increased plasma concentrations of CXCL10, IL6 and IL33 at age 9 were associated with persistently low trajectory from 8–30 years. These associations will be interrogated for causality with Mendelian Randomisation.