@article {1675296,
	title = {The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality},
	journal = {Am J Respir Crit Care Med},
	volume = {203},
	number = {9},
	year = {2021},
	month = {2021 May 01},
	pages = {1149-1157},
	abstract = {Rationale: The association between aging and idiopathic pulmonary fibrosis has been established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated.Objectives: To evaluate the associations among aging biomarkers, ILA, and all-cause mortality.Methods: In the FHS (Framingham Heart Study), we evaluated associations among plasma biomarkers (IL-6, CRP [C-reactive protein], TNFR [tumor necrosis factor α receptor II], GDF15 [growth differentiation factor 15], cystatin-C, HGBA1C [Hb A1C], insulin, IGF1 [insulin-like growth factor 1], and IGFBP1 [IGF binding protein 1] and IGFBP3]), ILA, and mortality. Causal inference analysis was used to determine whether biomarkers mediated age. GDF15 results were replicated in the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) Study.Measurements and Main Results: In the FHS, there were higher odds of ILA per increase in natural log-transformed GDF15 (odds ratio [95\% confidence interval], 3.4 [1.8-6.4]; P = 0.0002), TNFR (3.1 [1.6-5.8]; P = 0.004), IL-6 (1.8 [1.4-2.4]; P \< 0.0001), and CRP (1.7 [1.3-2.0]; P \< 0.0001). In the FHS, after adjustment for multiple comparisons, no biomarker was associated with increased mortality, but the associations of GDF15 (hazard ratio, 2.0 [1.1-3.5]; P = 0.02), TNFR (1.8 [1.0-3.3]; P = 0.05), and IGFBP1 (1.3 [1.1-1.7]; P = 0.01) approached significance. In the COPDGene Study, higher natural log-transformed GDF15 was associated with ILA (odds ratio, 8.1 [3.1-21.4]; P \< 0.0001) and mortality (hazard ratio, 1.6 [1.1-2.2]; P = 0.01). Causal inference analysis showed that the association of age with ILA was mediated by IL-6 (P \< 0.0001) and TNFR (P = 0.002) and was likely mediated by GDF15 (P = 0.008) in the FHS and was mediated by GDF15 (P = 0.001) in the COPDGene Study.Conclusions: Some aging-related biomarkers are associated with ILA. GDF15, in particular, may explain some of the associations among age, ILA, and mortality.},
	keywords = {Adult, Age Factors, Aged, Aging, Biomarkers, Female, Growth Differentiation Factor 15, Humans, Longitudinal Studies, Lung Diseases, Interstitial, Male, Middle Aged, Odds Ratio, Survival Rate},
	issn = {1535-4970},
	doi = {10.1164/rccm.202007-2993OC},
	author = {Sanders, Jason L and Putman, Rachel K and Dupuis, Jos{\'e}e and Xu, Hanfei and Murabito, Joanne M and Araki, Tetsuro and Nishino, Mizuki and Benjamin, Emelia J and Levy, Daniel and Ramachandran, Vasan S and Washko, George R and Curtis, Jeffrey L and Freeman, Christine M and Bowler, Russell P and Hatabu, Hiroto and O{\textquoteright}Connor, George T and Hunninghake, Gary M}
}