Chronic obstructive pulmonary disease (COPD) affects 212 million people globally and is responsible for 3 million premature deaths each year. Smoking causes most COPD, but it can also develop as a result of low lung function trajectory in childhood, adolescence and early adulthood. ALSPAC has been part of the effort to characterise such low lung function trajectories.

The mechanisms underlying low lung function trajectories remain unclear. One plausible mechanism is accelerated biological aging, which can be measured using epigenetic clocks based on DNA methylation data, or by measuring biomarkers of cellular senescence. Cellular senescence is an important pathological process in biological aging, in which cells stop dividing and secrete a variety of inflammatory mediators, leading to a state of chronic low-grade inflammation thought to be important in a variety of diseases, including COPD. The role of epigenetic aging and cellular senescence in low lung function trajectory and COPD is of interest because treatments which can arrest or reverse these processes are under investigation and could become COPD treatments in future.

This study will attempt to assess whether epigenetic age acceleration, calculated from DNA methylation data from blood samples collected from ALSPAC participants at age 7, is associated with belonging to a lower lung function (FEV1) trajectory. It will also assess for an association of plasma markers of cellular senescence (IL6, CXCL10, LAP TGF beta-1) with lung function trajectory. If observational associations are evident between epigenetic age acceleration or plasma markers of cellular senescence and lung function, multivariable mendelian randomisation analyses will be undertaken to assess whether they are likely to be causal.