Pathological implications of cell aging in vitro.
The replicative capacity of cultured human fibroblasts is discussed in relation to three areas, diabetes mellitus, expression of HL-A antigens, and interactions with polymerizing fibrin. The replicative capacity of cells is dimished in diabetes mellitus and certain related disorders such as progeria and Werner's syndrome, all of which feature accelerated aging. Expression of HL-A antigens is reduced in progeria fibroblasts compared to normal cultures at corresponding stages of passage. Normal cells show more subtle alteration during aging in vitro probably related to clonal heterogeneity and/or selection within mass cultures. Early-passage fibroblasts interact rapidly with polymerizing fibrin to form a mature clot which is then retracted by a process dependent on cellular integrity and active metabolism. Late-passage cultures are less active in both parameters as are fibroblasts from a subject with progeria. These observations, in total, may relate to altered self-recognition and certain autoimmune concomitants of aging in vivo. They may also help to explain impaired wound healing and increased predisposition to atherothrombosis in aging and diabetic individuals. This system of cultured human fibroblasts should serve as an excellent model to investigate the cellular and molecular basis of diabetes mellitus, aging and related pathology.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging; D002239:Carbohydrate Metabolism, Inborn Errors; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D002648:Child; D002999:Clone Cells / Q000276:immunology; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006680:HLA Antigens; D006801:Humans; D008954:Models, Biological; D011371:Progeria / Q000276:immunology / Q000378:metabolism; D014898:Werner Syndrome / Q000276:immunology / Q000378:metabolism
D006680:HLA Antigens; D005337:Fibrin; D005947:Glucose