EXPRESSION OF ENDOTHELIN, FIBRONECTIN, AND MORTALIN AS AGING AND MORTALITY MARKERS

Studies on fibronectin, endothelin-l, and mortalin from our laboratory are reviewed here. Fibronectin expression has been analyzed as upregu lated during in vitro serial passaging of human fetal lung and neonata l foreskin fibroblasts as well as umbilical vein endothelial cells. In vivo aging of skin fibroblasts, as well as aortic endothelial cells, are also accompanied by upregulation of fibronectin expression. Fibron ectin promoter binding proteins from young and old cell nuclear extrac ts were further explored by gel retardation assay. Preliminary analyse s have detected age-related differential binding activities with respe ct to AP-1, CRES, TFIID, CTF, and AP-2 regions, whereas Spl binding pr oteins remain unaltered. Endothelin-l expression is also seen as upreg ulated during in vitro and in vivo aging of endothelial cells. This ca n contribute to the hypertension commonly observed in elderly patients . Mortalin, a novel member of hsp70 family of proteins, was initially identified by virtue of its association with a cellular mortal phenoty pe. Subsequently, normal cells and the ones with an immortal phenotype have been found to have differential subcellular localization of this protein. Antiproliferative activity of this protein in normal cells a nd the deregulation of expression in transformed cells is observed whi ch suggests the association of mortalin in pathways that determine cel lular divisional phenotype. Copyright (C) 1997 Elsevier Science Inc.