Cellular Senescence in Idiopathic Pulmonary Fibrosis
Open accessAbstract
Cellular senescence (CS) is increasingly implicated in the etiology of age-related diseases. While CS can facilitate physiological processes such as tissue repair and wound healing, senescent cells also contribute to pathophysiological processes involving macromolecular damage and metabolic dysregulation that characterize multiple morbid and prevalent diseases, including Alzheimer's disease, osteoarthritis, atherosclerotic vascular disease, diabetes mellitus, and idiopathic pulmonary fibrosis (IPF). Preclinical studies targeting senescent cells and the senescence-associated secretory phenotype (SASP) with "senotherapeutics" have demonstrated improvement in age-related morbidity associated with these disease states. Despite promising results from these preclinical trials, few human clinical trials have been conducted. A first-in-human, open-label, pilot study of the senolytic combination of dasatinib and quercetin (DQ) in patients with IPF showed improved physical function and mobility. In this review, we will discuss our current understanding of cellular senescence, its role in age-associated diseases, with a specific focus on IPF, and potential for senotherapeutics in the treatment of fibrotic lung diseases.
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D+Q alleviates a range of age- and senescence-related disorders in mice and significantly improves lung function and exercise capacity with intermittent dosing at onset of bleomycin lung-injury.
“D + Q alleviates a range of age- and senescence-related disorders in mice,5,12,13,20, 21, 22, 23, 24 and has been found to significantly improve lung function and exercise capacity with intermittent dosing at onset of bleomycin lung-injury.5”
From Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability (2023) · cites this paper as [12]
The Senotherapeutics for IPF section reports significant improvements in physical and pulmonary function with DQ in bleomycin-induced fibrosis mouse models. The Senomorphics and Senolytics section also lists several preclinical benefits. Our copy does not say that dosing in the mouse model was intermittent or began at the onset of lung injury; its description of intermittent dosing concerns a human IPF trial. (LLM, conf=0.86)
Experimental — accuracy not yet measuredSenotherapeutic treatments that target cellular senescence have been accomplished in animal models and demonstrated improved functional status.
“Senotherapeutic treatments that target cellular senescence have been accomplished in animal models and demonstrated improved and functional status.12,13”
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Additional file 2 of NR2F2 alleviates pulmonary fibrosis by inhibition of epithelial cell senescence
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- Authors
- Kellogg, D. L., Kellogg, D. L., Musi, N., & Nambiar, A. M.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Nambiar, A. M.
- Venue
- Current Molecular Biology Reports
- Published
- 2021-08-12
- Volume
- 7
- Issue
- 3
- Pages
- 31-40
- ISSN
- 2198-6428 (ISSN-L)
- PMC
- PMC8358258
- OpenAlex
- W3194598144
- Cited by
- 67
- References
- 118
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 12 · 2023: 15 · 2022: 9 · 2021: 1
- FWCI
- 1.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Molecular Biology Reports (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P30AG044271)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- cellular senescence, idiopathic pulmonary fibrosis, senescence-associated secretory phenotype, senotherapeutics, senolytics, dasatinib, quercetin, age-related diseases, fibrotic lung disease, physical function
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