دورية أكاديمية
Biological Age, Chronological Age and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis.
| العنوان: | Biological Age, Chronological Age and Survival in Pulmonary Fibrosis: A Causal Mediation Analysis. |
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| المؤلفون: | Pugashetti JV; University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States; vupugash@med.umich.edu., Kim JS; University of Virginia, Medicine, Charlottesville, Virginia, United States.; Charlottesville, Virginia, United States., Bose S; University of Michigan Michigan Medicine, Department of Biostatistics, Ann Arbor, Michigan, United States., Adegunsoye A; University of Chicago Department of Medicine, Section of Pulmonary and Critical Care, Dept. of Medicine, Chicago, Illinois, United States., Linderholm AL; University of California Davis, Davis, California, United States., Chen CH; University of California Davis, Department of Internal Medicine, Davis, California, United States., Strek ME; The University of Chicago, Department of Medicine, Chicago, Illinois, United States., Flaherty KR; University of Michigan Michigan Medicine, Ann Arbor, Michigan, United States., Murray S; University of Michigan, Ann Arbor, Michigan, United States., Newton CA; The University of Texas Southwestern Medical Center, Internal Medicine, Dallas, Texas, United States.; The University of Texas Southwestern Medical Center, Dallas, Texas, United States., Alqalyoobi S; Brody School of Medicine at East Carolina University, Internal Medicine - Pulmonary, Critical Care and Sleep Medicine, Greenville, North Carolina, United States., Ma SF; University of Virginia School of Medicine, Division of Pulmonary & Critical Care Medicine, Charlottesville, Virginia, United States.; University of Virginia., Mychaleckyj JC; University of Virginia, Center for Public Health Genomics, Department of Public Health Sciences, Charlottesville, Virginia, United States., Bowler RP; National Jewish Health, Department of Medicine, Denver, Colorado, United States., Han MK; University of Michigan, Pulmonary & Critical Care, Ann Arbor, Michigan, United States., Curtis JL; University of Michigan Health System, Internal Medicine, Ann Arbor, Michigan, United States.; VA Ann Arbor Healthcare System, Medical Service, Ann Arbor, Michigan, United States., Martinez FJ; Weill Cornell Medicine, New York, New York, United States., Smith JA; University of Michigan, Epidemiology, Ann Arbor, Michigan, United States., Noth I; University of Virginia, Division of Pulmonary and Critical Care Medicine, Charlottesville, Virginia, United States., Oldham JM; University of California Davis, Pulmonary and Critical Care Medicine, Davis, California, United States. |
| المصدر: | American journal of respiratory and critical care medicine [Am J Respir Crit Care Med] 2024 Jun 06. Date of Electronic Publication: 2024 Jun 06. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Thoracic Society Country of Publication: United States NLM ID: 9421642 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1535-4970 (Electronic) Linking ISSN: 1073449X NLM ISO Abbreviation: Am J Respir Crit Care Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : New York, NY : American Thoracic Society Original Publication: New York, NY : American Lung Association, c1994- |
| مستخلص: | Rationale: Accelerated biological aging has been implicated in the development of interstitial lung disease (ILD) and other diseases of aging but remains poorly understood. Objectives: To identify plasma proteins that mediate the relationship between chronological age and survival association in patients with ILD. Methods: Causal mediation analysis was performed to identify plasma proteins that mediated the chronological age-survival relationship in an idiopathic pulmonary fibrosis (IPF) discovery cohort. Proteins mediating this relationship after adjustment for false discovery were advanced for testing in an independent ILD validation cohort and explored in a chronic obstructive pulmonary disease (COPD) cohort. A proteomic-based measure of biological age was constructed and survival analysis performed assessing the impact of biological age and peripheral blood telomere length on the chronological age-survival relationship. Results: Twenty-two proteins mediated the chronological age-survival relationship after adjustment for false discovery in the IPF discovery cohort (n=874), with nineteen remaining significant mediators of this relationship in the ILD validation cohort (n=983) and one mediating this relationship in the COPD cohort. Latent transforming growth factor beta binding protein 2 and ectodysplasin A2 receptor showed the strongest mediation across cohorts. A proteomic measure of biological age completely attenuated the chronological age-survival association and better discriminated survival than chronological age. Results were robust to adjustment for peripheral blood telomere length, which did not mediate the chronological age-survival relationship. Conclusions: Molecular measures of aging completely mediate the relationship between chronological age and survival, suggesting that chronological age has no direct effect on ILD survival. |
| معلومات مُعتمدة: | U01 HL137880 United States HL NHLBI NIH HHS |
| فهرسة مساهمة: | Keywords: Age; Causal Mediation; Idiopathic Pulmonary Fibrosis; Proteomics |
| تواريخ الأحداث: | Date Created: 20240606 Latest Revision: 20240629 |
| رمز التحديث: | 20240629 |
| DOI: | 10.1164/rccm.202310-1887OC |
| PMID: | 38843133 |
| قاعدة البيانات: | MEDLINE |
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