scholarly journals Breathing Well Across the Lifespan: Pulmonary Aging and Geroscience-Targeted Therapies

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 749-749
Author(s):  
Jason Sanders
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Pulmonary Diseases ◽  
Human Populations ◽  
Aging Research ◽  
Novel Treatments ◽  
Organ Specific ◽  
Nutrient Signaling ◽  
Telomere Biology ◽  
Increased Susceptibility

Abstract Excellent pulmonary function is one of the strongest predictors of longevity across animal models and human populations. Unfortunately, none of the major age-associated pulmonary diseases – obstructive lung disease, pulmonary fibrosis, and increased susceptibility to pneumonia – have strongly effective disease modifying therapies. There is growing evidence that normal age-associated decline in pulmonary function and major age-associated pulmonary diseases are linked to the hallmarks of aging including senescence, nutrient signaling dysregulation, mitochondrial dysfunction, and telomere disorders. This presents opportunities for collaboration between gerontologists and pulmonologists to unravel age-associated developmental mechanisms and design novel treatments. In this symposium, leaders in pulmonary aging research will present novel data on links between aging and pulmonary health and geroscience-based interventions under study. Dr. Sanders will provide an overview of the scientific and clinical space and present epidemiologic associations between aging biomarkers, early pulmonary fibrosis, and mortality. Dr. Le Saux will discuss senescence and specifically how eicosanoid biology may explain organ-specific patterns of senescence-associated fibrosis. Dr. Thannickal will discuss age-associated perturbations in metabolism and mitochondrial function and targeting these pathways to improve lung function and treat pulmonary diseases. Dr. Newton will discuss mechanisms and clinical applications of telomere biology to pulmonary aging. Symposium attendees will (1) be poised to generate collaborations between gerontologists and pulmonologists to address existing knowledge gaps in mechanisms of pulmonary aging, and (2) develop a better understanding of translational opportunities to design geroscience-based diagnostics and therapeutics to improve pulmonary health with aging.

scholarly journals Prognostic significance of pulmonary function tests in dyskeratosis congenita, a telomere biology disorder

2019 ◽  
Vol 5 (4) ◽  
pp. 00209-2019 ◽  
Author(s):  
Neelam Giri ◽  
Sandhiya Ravichandran ◽  
Youjin Wang ◽  
Shahinaz M. Gadalla ◽  
Blanche P. Alter ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Pulmonary Disease ◽  
Cumulative Incidence ◽  
Pulmonary Function Tests ◽  
Dyskeratosis Congenita ◽  
Telomere Maintenance ◽  
Genetic Characteristics ◽  
Function Tests ◽  
Telomere Biology

Pulmonary fibrosis and pulmonary arteriovenous malformations are known manifestations of dyskeratosis congenita (DC), a telomere biology disorder (TBD) and inherited bone marrow failure syndrome caused by germline mutations in telomere maintenance genes resulting in very short telomeres. Baseline pulmonary function tests (PFTs) and long-term clinical outcomes have not been thoroughly studied in DC/TBDs.In this retrospective study, 43 patients with DC and 67 unaffected relatives underwent baseline PFTs and were followed for a median of 8 years (range 1–14). Logistic regression and competing risk models were used to compare PFT results in relation to clinical and genetic characteristics, and patient outcomes.Restrictive abnormalities on spirometry and moderate-to-severe reduction in diffusing capacity of the lung for carbon monoxide were significantly more frequent in patients with DC than relatives (42% versus 12%; p=0.008). The cumulative incidence of pulmonary disease by age 20 years was 55% in patients with DC with baseline PFT abnormalities compared with 17% in those with normal PFTs (p=0.02). None of the relatives developed pulmonary disease. X-linked recessive, autosomal recessive inheritance or heterozygous TINF2 variants were associated with early-onset pulmonary disease that mainly developed after haematopoietic cell transplantation (HCT). Overall, seven of 14 patients developed pulmonary disease post-HCT at a median of 4.7 years (range 0.7–12). The cumulative incidence of pulmonary fibrosis in patients with heterozygous non-TINF2 pathogenic variants was 70% by age 60 years.Baseline PFT abnormalities are common in patients with DC and associated with progression to significant pulmonary disease. Prospective studies are warranted to facilitate clinical trial development for patients with DC and related TBDs.

scholarly journals Identification of Key Candidate Genes Involved in the Progression of Idiopathic Pulmonary Fibrosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1123
Author(s):  
Yu Cui ◽  
Jie Ji ◽  
Jiwei Hou ◽  
Yi Tan ◽  
Xiaodong Han
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Candidate Genes ◽  
Expression Profiles ◽  
Biological Processes ◽  
Protein Protein Interaction ◽  
Novel Treatments ◽  
Kegg Pathway Analysis ◽  
Cell Components ◽  
Upregulated Genes

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein–protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.

scholarly journals Preliminary Analysis of the Therapeutic Mechanism of Feiluoning in Convalescent Patients With COVID-19

2020 ◽  
Vol 15 (12) ◽  
pp. 1934578X2097762
Author(s):  
Zongchao Hong ◽  
Maolin Hong ◽  
Bo Liu ◽  
Ying Zhang ◽  
Yanfang Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Target Genes ◽  
Interaction Analysis ◽  
Binding Capacity ◽  
Chemical Constituents ◽  
The Core ◽  
Target Network ◽  
Compound Target

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), is often accompanied by injury to pulmonary function and pulmonary fibrosis. Feiluoning (FLN) is a new Chinese medicine prescription which is available for the treatment of severe and critical convalescence of COVID-19 patients. FLN also has a positive effect on pulmonary function injury and pulmonary fibrosis. We explored the potential mechanism of FLN’s effect on the convalescent treatment of COVID-19. According to the pharmacodynamic activity parameters, we screened the active chemical constituents of FLN by comparing the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The Uniprot database was used to querying the corresponding target genes, and Cytoscape 3.6.1 was used to construct a herb-compound-target network. Protein interaction analysis, target gene function enrichment analysis, and signal pathway analysis were performed using the STRING, DAVID, and Kyoto Encyclopedia of Genes and Genomes pathway databases. Molecular docking was used to predict the binding capacity of the core compound with COVID-19 hydrolase 3 Cl and angiotensin-converting enzyme 2 (ACE2). The herb-compound-target network was successfully constructed and key targets identified, including prostaglandin G/H synthase 2, estrogen receptor 1, heat shock protein HSP 90, and androgen receptor. The major affected metabolic pathways were pathways in cancer, pancreatic cancer, nonsmall cell lung cancer, and toll-like receptor signaling. The core compounds of FLN, including quercetin, luteolin, kaempferol, and stigmasterol, could strongly bind to COVID-19 3 Cl hydrolase, and other compounds, including 7-O-methylisomucronulatol and medicocarpin, could strongly bind to ACE2. Thus, it is predicted that FLN has the characteristics of a multicomponent, multitarget, and multichannel overall control compound. FLN’s mechanism of action in the treatment of COVID-19 may be associated with the regulation of inflammation and immune-related signaling pathways, and the influence of COVID-19 3 Cl hydrolase binding ability.

scholarly journals Annual changes in pulmonary function in combined pulmonary fibrosis and emphysema: Over a 5-year follow-up

2013 ◽  
Vol 107 (12) ◽  
pp. 1986-1992 ◽  
Author(s):  
Yoshiaki Kitaguchi ◽  
Keisaku Fujimoto ◽  
Ryoichi Hayashi ◽  
Masayuki Hanaoka ◽  
Takayuki Honda ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Annual Changes

Pulmonary Function Tests and Idiopathic Pulmonary Fibrosis

CHEST Journal ◽  
1997 ◽  
Vol 111 (1) ◽  
pp. 7-8 ◽  
Author(s):  
Steven H. Kirtland ◽  
Richard H. Winterbauer
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Function ◽  
Pulmonary Function Tests ◽  
Function Tests

scholarly journals Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics

2021 ◽  
Vol 12 ◽  
Author(s):  
Pamela Velázquez-Díaz ◽  
Erika Nakajima ◽  
Parand Sorkhdini ◽  
Ashley Hernandez-Gutierrez ◽  
Adam Eberle ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Oculocutaneous Albinism ◽  
Alveolar Epithelial Cells ◽  
Multisystem Disorder ◽  
Alveolar Epithelial ◽  
Novel Treatments ◽  
Molecular Approaches ◽  
Hermansky Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.

Telomerase-Positive Somatic Tissues of Honeybee Queens (Apis mellifera) Display No DNA Replication

2021 ◽  
pp. 1-6
Author(s):  
Justina Koubová ◽  
Radmila Čapková Frydrychová
Keyword(s):  
Apis Mellifera ◽  
Dna Replication ◽  
Cell Types ◽  
Telomerase Activity ◽  
Protective Mechanism ◽  
Aging Research ◽  
Telomere Attrition ◽  
Eusocial Insects ◽  
Somatic Tissues ◽  
Telomere Biology

Telomere biology is closely linked to the process of aging. The restoration of telomere length by maintaining telome­rase activity in certain cell types of human adults allows for the proliferative capacity of the cells and preserves the regeneration potential of the tissue. The absence of telome­rase, that leads to telomere attrition and irreversible cell cycle arrest in most somatic cells, acts as a protective mechanism against uncontrolled cancer growth. Nevertheless, there have been numerous studies indicating noncanonical functions of telomerase besides those involved in telomere lengthening. Eusocial insects serve as a great system for aging research. This is because eusocial reproductives, such as queens and kings, have a significantly extended lifespan compared to nonreproductive individuals of the same species. We report that the somatic tissues of honeybee queens (<i>Apis mellifera</i>) are associated with upregulated telomerase activity; however, this upregulation does not fully correlate with the rate of DNA replication in the tissues. This indicates a noncanonical role of telomerase in the somatic tissues of honeybee queens.

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