title: Impaired migration, integrin function, and actin cytoskeletal organization in dermal fibroblasts from a subset of aged human donors.
abstract: Deficits in the motility of fibroblasts contribute to age-related impairment of wound healing. We analyzed 'young' fibroblasts from four healthy donors 22-30 years old and 'aged' fibroblasts from six healthy donors 81-92 years old for migratory ability on type I collagen, secretion of matrix metalloproteases (MMPs), attachment to matrices and, expression and function of integrin alpha2beta1. Cells from each donor were analyzed separately in each experiment. Whereas migration of young fibroblasts was uniformly robust, three aged lines migrated well and three migrated poorly. Synthesis of MMP1 and TIMP1, but not MMP2 or MMP9, was increased in the aged fibroblasts relative to the young fibroblast lines irrespective of their motility. All lines of young and aged fibroblasts attached to plastic or collagen with similar efficiency. Although young and aged fibroblasts expressed comparable levels of the alpha2 integrin; the lines of aged fibroblasts that were poor migrators exhibited a significant reduction in alpha2beta1 function relative to fibroblasts with normal migratory capacities. Moreover, the lines of aged fibroblasts that exhibited poor migration demonstrated a disordered actin cytoskeleton and a reduced ability to contract collagen gels. In conclusion, 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 and reduced alpha2beta1 function.
authors.affiliation: Division of Gerontology and Geriatric Medicine, Box 359755, Department of Medicine, University of Washington, Seattle, WA 98104, USA. mjr@u.washington.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Reed
authors.forename: N S
authors.initials: NS
authors.lastname: Ferara
authors.forename: R B
authors.initials: RB
authors.lastname: Vernon
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005782:Gels; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000502:physiology; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D038981:Receptors, Collagen; D012867:Skin / Q000166:cytology; D015595:Skin Aging / Q000502:physiology; D014019:Tissue Donors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
chemical_list: D000199:Actins; D005782:Gels; D016023:Integrins; D038981:Receptors, Collagen; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D020782:Matrix Metalloproteinases