We show that genes TNFRSF12A and CD38 encode factors previously unrecognized as COPD contributors, and have generated the model that explains accelerated aging phenotypes previously observed in COPD patients, and calls for investigation of the balance of TNFRSF12A/CD38 proteins as the key to establishing vicious cycle of unresolvable tissue remodeling in COPD lungs. This evidence concerns the gene TNFRSF12A and chronic obstructive pulmonary disease.