Barrier breakdown in ageing and age-related diseases: The potential role of hierarchical epigenetic control of microRNAs on surfactant collectins, S100 alarmins and fibronectin

Surfactant proteins, particularly SP-A and SP-D, S100 family members and fibronectin belong to the group of socalled stress-related molecules and share the characteristic of being expressed at anatomical barriers such as the skin, pulmonary/respiratory epithelia, and the intestinal tract. In this context, they constitute part of the body’s first line of defence, acting in concert with immune cells to counter a broad spectrum of external and internal stressors (exposomes), potentially fuelling chronic low-grade inflammation (inflammaging). The levels of the above-mentioned molecules in the blood or local tissues result altered in a range of age-associated pathologies and have been proposed as potential diagnostic/prognostic biomarkers, although they generally lack specificity for a single pathological condition. Evidence from in silico analyses further suggests that most of these molecules may be regulated by members of the microRNA-29 family, pointing towards hierarchical epigenetic mechanisms that merit detailed investigation as potential contributors to ageing-related biomarker signatures. Despite research advances, the identification of robust biomarkers capable of predicting disease onset at the individual level, an essential prerequisite for precise geromedicine, remains an elusive goal in clinical practice. Although individuals differ biologically, this does not preclude the existence of overarching principles that could be reflected in hierarchical biomarkers. Within this framework, a pragmatic strategy for immediate application may involve the systematic use of currently available longitudinal data, for example, from hospitalised patients or through dedicated software programs utilised by general practitioners.