Pharmacotherapies for Ageing Lungs

Population aging is reshaping the landscape of respiratory disease, with COPD, idiopathic pulmonary fibrosis, bronchiectasis, asthma and lung cancer increasingly concentrated in older adults who also carry a heavy burden of cardiovascular and metabolic comorbidities. Aging lungs exhibit structural decline, extracellular matrix remodeling, mitochondrial dysfunction and accumulation of senescent cells, driving chronic inflammation, fibrosis, impaired host defence and reduced resilience to acute insults. Current pharmacotherapies (long acting bronchodilators and inhaled corticosteroids, antifibrotics such as pirfenidone and nintedanib, long term macrolides, and targeted or immune based treatments for lung cancer), have improved outcomes but were not explicitly developed for aging biology, multimorbidity or polypharmacy. In parallel, an emerging “geroscience guided” pharmacology of the lung is taking shape, including senotherapies (senolytics and senomorphics), pathway specific antifibrotics (e.g., IL 11, TNIK, PI3K/Akt), mitochondrial and autophagy modulators, and innovative cell and gene based approaches that target senescent alveolar cells and age associated fibrosis.

The aim of this Research Topic in the Respiratory Pharmacology section is to attract mechanistic and translational work that: evaluates the efficacy, safety and pharmacokinetics/pharmacodynamics of established respiratory drugs in older adults and in multimorbid settings; explores novel small molecules, biologics, senotherapeutics and drug delivery systems that specifically target cellular senescence, inflammaging, extracellular matrix remodeling and mitochondrial dysfunction in chronic and acute lung diseases; and identifies shared targets and pharmacological strategies that can support a shift from purely disease centred treatment towards mechanism and aging centred pharmacotherapy of the lung.

This collection will welcome studies focused on (but not limited to):

o Bronchodilator and ICS pharmacology in older adults PK/PD, safety and adherence of LAMA/LABA and ICS (alone or in combination) in elderly patients with COPD and asthma, including inhaler devices and real world effectiveness.

o Antifibrotic drugs and novel antifibrosis pathways Clinical and experimental studies on pirfenidone, nintedanib and emerging antifibrotic agents (e.g., TNIK, IL 11, CB1R, PI3K/Akt targets) in age associated ILD and pulmonary fibrosis.

o Senotherapies in chronic lung disease Small molecules, biologics and combinations that clear or reprogram senescent cells in COPD, IPF, bronchiectasis and lung cancer, and their impact on SASP, remodeling and repair.

o Mitochondria and autophagy targeted pharmacology Agents modulating AMPK–Sirt1, PINK1/Parkin, oxidative stress and mitochondrial dynamics in aging lungs, ALI/ARDS and chronic respiratory disease.

o NAD⁺ augmentation and metabolic-rejuvenation therapies Pharmacological and nutritional strategies that restore NAD⁺ pools and improve mitochondrial energy metabolism in aging lung progenitor cells, including NAD⁺ precursors (NR, NMN), CD38 inhibitors, PARP modulators, and SIRT1/SIRT3-targeted interventions, with emphasis on epithelial regeneration, redox balance, and resistance to metabolic exhaustion.

o Alveolar-vascular interface repair and AT1 cell rejuvenation Mechanisms of age-related AT1 cell exhaustion, impaired gas-exchange capacity, and disrupted AT1–endothelial cross-talk, along with pharmacologic, metabolic, and regenerative approaches (e.g., VEGF/VEGFR modulation, mechanotransduction pathways, endothelial niche restoration, AT1 lineage stabilization) designed to enhance alveolar barrier integrity and alveolar–capillary air-exchange efficiency in the aging lung.

o Traditional medicines and phytotherapeutics with anti aging lung effects Pharmacological characterisation of compounds such as Lianhua Qingke, Maimendong decoction, tetrandrine, Bazibushen and related preparations in models of senescence, fibrosis and inflammation.

o Immunomodulators, biologics and immune checkpoint therapies in the elderly Benefit–risk profiles of biologics for asthma and autoimmune lung disease, management of immune checkpoint inhibitor related lung toxicity, and the role of immunosenescence.

o Systemic comorbidities and pleiotropic drugs affecting lung aging Effects of cardiovascular and metabolic agents (e.g., statins, SGLT2 inhibitors, GLP 1 receptor agonists, antihypertensives) on pulmonary outcomes, vascular aging in the lung and drug–drug interactions.

o Regenerative and advanced pharmacological approaches Cell and gene therapies (e.g., GDF11 secreting cells, recombinant CC16, gene editable nanoplatforms), biomaterials and targeted delivery systems designed to rejuvenate or repair aging lung tissue.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Technology and Code

Keywords: Aging Lung, COPD, Idiopathic Pulmonary Fibrosis, Asthma in Older Adults, Lung Cancer, Interstitial Lung Disease, Cellular Senescence, Oxidative Stress, Autophagy

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.