This document provides materials and methods related to PAPP-A polypeptides, aging, and transgenic non-human mammals whose genomes comprise a disrupted PAPP-A allele. Methods for making such transgenic non-human mammals, and using them and other mammals to identify and characterize agents that affect conditions related to PAPP-A activity, such as vascular restenosis, atherosclerosis, wound healing, cancer, fibrosis, bone development, fetal development, longevity, and fracture repair, also are provided.