title: Senescent Cells Impair Erectile Function through Induction of Endothelial Dysfunction and Nerve Injury in Mice.
abstract: Erectile dysfunction (ED) is a major health problem, particularly in the elderly population, which is rapidly increasing. It is necessary to elucidate the mechanism by which ED occurs in the elderly. Cellular senescence is commonly detected in old tissues, and it is well known that senescent cells not only withdraw from the cell cycle but also remain viable and actively produce a variety of cytokines. We examined the effect of senescent cells on erectile function after injection of senescent cells into the penises of mice. Human umbilical vein endothelial cells were infected with an adenovirus expressing a constitutively active mutant of Ras to induce senescence, and were injected into the penises of nude mice. These senescent cells expressed proinflammatory cytokines such as interleukin-1β (IL-1β). Injection of senescent cells impaired erectile function, as assessed by the measurement of intracavernous pressure. Although the structure of the cavernous body did not remarkably change, expression of the catalytically active form of endothelial nitric oxide synthase and that of total neural nitric oxide synthase significantly decreased after injection. The penises injected with the senescent cells expressed human IL-1β and subsequently endogenous proinflammatory cytokines such as mouse IL-1β and tumor necrosis factor-α. These results suggested that senescent cells impaired erectile function through induction of endothelial dysfunction and nerve injury. These effects may be mediated by proinflammatory cytokines produced by senescent cells.
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimatsu
authors.affiliation: Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki, Japan.
authors.forename: Etsu
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yasuho
authors.initials: Y
authors.lastname: Saito
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Niimi
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nomiya
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuhara
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: The Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology*; D007172:Erectile Dysfunction / Q000628:therapy*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009420:Nervous System / Q000473:pathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III