title: [Antisenescence as a novel therapeutic strategy for vascular aging].
abstract: Vascular cells have a finite lifespan when cultured in vitro and eventually enter an irreversible growth arrest state called "cellular senescence." It has been reported that many of the changes in senescent vascular cell behavior are consistent with the changes seen in age-related vascular diseases. Recently, senescent vascular cells have been demonstrated in human atherosclerotic lesions but not non-atherosclerotic lesions. Moreover, these cells express increased levels of proinflammatory molecules and decreased levels of endothelial nitric oxide synthase, suggesting that cellular senescence in vivo contributes to the pathogenesis of human atherosclerosis. One widely discussed hypothesis of senescence is the telomere hypothesis. An increasing body of evidence has established the critical role of the telomere in vascular cell senescence. More recent evidence suggests that telomere-independent mechanisms are implicated in vascular cell senescence. Activation of Ras, an important signaling molecule involved in atherogenic stimuli, induces vascular cell senescence and thereby promotes vascular inflammation in vitro and in vivo. Constitutive activation of Akt also induces vascular cell senescence. This novel role of Akt in regulating the cellular lifespan may contribute to various human diseases including atherosclerosis and diabetes mellitus. Although a causal link between vascular aging and vascular cell senescence remains elusive, a large body of data is consistent with cellular senescence contributing to age-associated vascular disorders. This review considers the clinical relevance of vascular cell senescence in vivo and discusses the potential of antisenescence therapy for human atherosclerosis.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine.
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology
chemical_list: D018799:Intercellular Adhesion Molecule-1