An 87-protein 'Accelerated Aging' score was independently associated with increased mortality (OR 1.07; 95% CI 1.03-1.11; p=0.001) and multiorgan dysfunction in tobacco-exposed adults.
Observational (n=1,084)
Yes
Does a proteomics-based accelerated aging score associate with multiorgan dysfunction and mortality in tobacco-exposed adults?
A proteomics-based accelerated aging score is independently associated with mortality and multiorgan dysfunction, including coronary and aortic calcification, in tobacco-exposed adults.
Effect estimate: OR 1.07 (95% CI 1.03-1.11)
p-value: p=0.001
Abstract Introduction Chronic obstructive pulmonary disease (COPD) is heterogeneous, with clusters of co-occurring conditions contributing to a multimorbid syndrome. COPD is more prevalent among individuals over 60 years of age and is marked by increased cellular senescence, oxidative stress, and inflammageing—hallmarks of biologic aging. Circulating proteomic signatures quantify biologic aging across organ systems and have been associated with aging-related phenotypes and outcomes. We hypothesized that a biologic aging endotype, with distinct protein mediator expression, associates with multiorgan dysfunction and mortality in COPD. Methods We analyzed Phase 1 Genetic Epidemiology of COPD (COPDGene) data, a multicenter observational study of tobacco-exposed adults. Plasma concentrations of 1,306 proteins from 1,084 participants were measured by SomaLogic SomaScan. We used LASSO (Least Absolute Shrinkage and Selection Operator) regression with adaptive selection to estimate a continuous composite “Biologic Age” from proteomic data. The model retained 87 proteins, with r = 0.88 and R2=0.77 for predicted versus chronologic age (p 0.001). “Accelerated Aging” was defined as the difference between predicted “Biologic Age” and chronologic age, with positive values indicating higher predicted biologic than chronologic age. We used logistic and linear regression analyses to evaluate the associations between “Accelerated Aging” and mortality, BODE index, MMRC dyspnea score, 6-minute walk distance (meters), FEV1% predicted, and CT measures of emphysema (%LAA-950), aortic and coronary calcification (Agatston scores), and musculoskeletal disease (HU). Results Among 1,084 tobacco-exposed individuals (median age 62, IQR 54-69 years; 49% male; 39% current smoker; median FEV1% predicted 84%, IQR 62-100%; 529 with COPD), the 87-protein “Biologic Aging” endotype (Figure 1a) included proteins implicated in aging biology (GDF-15, SOST, and MMP-12). “Accelerated Aging” independently associated with increased mortality (OR 1.07, 95%CI 1.03-1.11, p = 0.001), with stronger effect in those without COPD (OR 1.08, 95%CI 1.01-1.16, p = 0.026). In those with COPD, “Accelerated Aging” associated with higher BODE index (ß=0.06, p = 0.04), shorter 6-minute walk distance (ß=-15.3, p = 0.001), decreased FEV1% predicted (ß=-0.65, p = 0.01), increased emphysema (ß=0.48, p = 0.001), reduced pectoralis muscle density (ß=-1.36, p = 0.01), and increased aorta (ß=223.41, p = 0.000) and coronary artery calcification (ß=0.20, p = 0.001). In the non-COPD cohort, “Accelerated Aging” associated only with aorta calcification (ß=84.76, p = 0.001; Figure 1b). Conclusion We derived a “Biologic Age” endotype of 87 plasma proteins and developed a chronologic-age independent “Accelerated Aging” score reflecting biologic aging. Among those with COPD, “Accelerated Aging” independently associates with multiorgan dysfunction, functional impairment, and mortality. Validation in independent cohorts may establish proteomic aging metrics as integrative biomarkers for risk stratification. This abstract is funded by: T32HL007563 and by NHLBI grants U01 HL089897 and U01 HL089856 and by NIH contract 75N92023D00011.
Yang et al. (Fri,) conducted a observational in Chronic obstructive pulmonary disease (COPD) (n=1,084). Accelerated Aging score (proteomic biologic age) was evaluated on Mortality (OR 1.07, 95% CI 1.03-1.11, p=0.001). An 87-protein 'Accelerated Aging' score was independently associated with increased mortality (OR 1.07; 95% CI 1.03-1.11; p=0.001) and multiorgan dysfunction in tobacco-exposed adults.