Ageing-driven mechanisms and innovative therapies in fibrosing pulmonary diseases

Pulmonary fibrosis research is increasingly focused on the diverse mechanisms underlying disease progression, with attention shifting beyond immune cell biology towards the broader landscape of ageing-associated tissue remodeling and fibrogenesis. While chronic inflammation and immune dysfunction are pivotal contributors, accumulating evidence points to cellular senescence, mitochondrial dysfunction, epigenetic alterations, and metabolic reprogramming as equally significant drivers, particularly in the context of age-related interstitial lung disease. Hallmarks of ageing, such as impaired regenerative capacity, altered extracellular matrix signaling, and the accumulation of senescent cells, orchestrate complex interactions that foster a profibrotic environment and may account for therapeutic resistance and disease heterogeneity seen in older patients. Despite the increasing possibilities of anti-fibrotic interventions, a comprehensive understanding of how ageing biology and immunological events combine to provoke ongoing fibrotic mechanisms remains incomplete.Recent studies have illustrated key signaling cascades, such as TGF-β, Wnt/β-catenin, and senescence associated factors, that bridge the gap between immune responses and ageing-driven fibrosis. Novel preclinical models—incorporating both senescence and chronic injury—have exposed targets for intervention, while clinical trials exploring senescence or metabolic modulators, and epigenetic therapies offer hope for more robust disease modification. The current gaps include a limited catalogue of biomarkers discriminating ageing-driven from immune-driven pathology, and a lack of consensus on therapeutic endpoints in aged populations with fibrotic lung disease.This Research Topic aims to advance the field by bringing together new insights into the mechanisms through which senescence and associated or parallelly observed cellular processed influence pulmonary fibrosis, alongside the development of targeted therapies for prevention and intervention.To gather further insights into age-related mechanisms, integrative pathogenesis, and cutting-edge therapies in fibrotic lung disease, we welcome articles addressing, but not limited to, the following themes:o Cellular senescence and its mediators in lung fibrosiso Ageing-related alterations in fibroblast function and matrix remodelingo Metabolic and epigenetic reprogramming during fibrosis progressiono Emerging therapeutics: senolytics, epigenetic and metabolic modulatorso Biomarker discovery for ageing-driven fibrotic pathologyo Interaction of ageing and immune pathways in disease exacerbation and treatment responseo Preclinical and clinical trial results targeting ageing mechanismso Preventive strategies and interventions tailored for older patientsPlease note that Dr. Elizabeth Volkmann is consulting for Abbvie, GSK, Boehringer Ingelheim, Novartis, BMS; Speaking for Boehringer Ingelheim, Merck; Grants from Boehringer Ingelheim, GSK, Kadmon, Horizon, Prometheus, AstraZeneca.Please note that Dr. Veronika Müller is consulting Astra Zeneca, Actelion, Boehringer Ingelheim, Berlin-Chemie Menarini, BMS, Chiesi, Gilead, Lilly, MSD, Novartis, Richter, Roche, Sanofi, TEVA, Medison pharma.Please note that Dr. Scott Matson is a consultant and advisory board member for Boehringer Ingelheim and Bristol Myers Squibb. Topic editors: Veronika Müller, Elizabeth Volkmann, Swati Dabral Source: https://www.frontiersin.org/research-topics/79398/ageing-driven-mechanisms-and-innovative-therapies-in-fibrosing-pulmonary-diseases