Pulmonary Function Modulates Epigenetic Age in Subjects with Cystic Fibrosis.

Cystic fibrosis (CF) is the most common severe autosomal recessive disease among Caucasians. Modulators of cystic fibrosis transmembrane conductance regulator (CFTR) mutated protein significantly improved the outcome of subjects with CF. In the present study, we studied epigenetic age, applying the Horvath clock model, in 52 adult subjects with CF, all treated with elexacaftor/tezacaftor/ivacaftor (ETI). At baseline (T0), we found that half of the subjects have a significantly accelerated epigenetic age and a worse lung function, evaluated by forced expiratory volume in one second (FEV1). One year of ETI therapy (T1) impacted both the parameters, indicating that therapy with modulators must be started early, particularly in CF subjects with impaired lung function. The second group of CF subjects had an epigenetic age lower than the chronological one at T0 and lung function was better maintained. In these subjects, ETI therapy further improved lung function and tended to increase the epigenetic age, possibly improving metabolic functions and the general state of well-being. This also translates into an increase in the physical activities of a group of subjects who, before the therapy, had grown up under a glass bell. The analysis of epigenetic age may represent a potential biomarker to assess the individual outcome of the therapy in subjects with CF, although long-term studies need to evaluate it.