Impaired migration, integrin function, and actin cytoskeletal organizationin dermal fibroblasts from a subset of aged human donors

Deficits in the motility of fibroblasts contribute to age-related impairmen t of wound healing. We analyzed 'young' fibroblasts from four healthy donor s 22-30 years old and 'aged' fibroblasts from six healthy donors 81-92 year s old for migratory ability on type I collagen, secretion of matrix metallo proteases (MMPs), attachment to matrices and, expression and function of in tegrin alpha2 beta1. Cells from each donor were analyzed separately in each experiment. Whereas migration of young fibroblasts was uniformly robust, t hree aged lines migrated well and three migrated poorly. Synthesis of MMPI and TIMP1, but not MMP2 or MMP9, was increased in the aged fibroblasts rela tive to the young fibroblast lines irrespective of their motility. All line s of young and aged fibroblasts attached to plastic or collagen with simila r efficiency. Although young and aged fibroblasts expressed comparable leve ls of the alpha2 integrin; the lines of aged fibroblasts that were poor mig rators exhibited a significant reduction in alpha2 beta1 function relative to fibroblasts with normal migratory capacities. Moreover, the lines of age d fibroblasts that exhibited poor migration demonstrated a disordered actin cytoskeleton and a reduced ability to contract collagen gels. In conclusio n, aged fibroblasts, unlike young fibroblasts, displayed variable migratory capacities. Deficient migration by specific lines of aged fibroblasts was not related to the capacity to attach, express alpha2 integrin, or secrete MMPs and TIMP1, but was characterized by disorganized cytoskeletal actin an d reduced alpha2 beta1 function. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.