Ivette Buendía-Roldán1, Nancy Machuca1, Mayra Mejía1, Mariel Maldonado1, Annie Pardo2 & Moisés Selman1 Interstitial lung abnormalities (ILA) represent aging-associated bilateral interstitial abnormalities in nondependent areas of the lung. However, the aging mechanisms associated with ILA remain uncertain. α-Klotho is an anti-aging molecule that decreases progressively with age, and abnormally low circulating levels of this protein have been revealed in several chronic-degenerative diseases. In this study, we evaluated α-Klotho serum concentrations in individuals with ILA, and examined whether its levels were associated with pulmonary function decline. α-Klotho was measured by ELISA in 50 respiratory asymptomatic adults with ILA and 150 healthy individuals over 60 years. Compared with controls, ILA subjects were predominantly older males, and showed lower lung diffusing capacity (DLCO), higher desaturation after exercise, and higher concentrations of serum matrix metalloprotease-7 (6.24 ± 4.1 versus 4.3 ± 1.7 ng/ml; p = 0.002). No differences were found in serum concentrations of α-Klotho. However, lower levels of this protein in ILA significantly correlated with lower values of forced vital capacity (Rho = 0.39; p = 0.005), forced expiratory volume in one second (Rho = 0.39; p = 0.005), and DLCO (Rho = 0.29, p = 0.04). These findings suggest that decreased concentrations of α-Klotho may be a predictive biomarker of accelerated decline of lung function in individuals with ILA.