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.
Highlights
Erectile dysfunction (ED) is a major global health concern and affects more than 10 million Japanese males [1]
We have recently demonstrated that human umbilical vein endothelial cells (HUVECs) produce cytokines such as interleukin-1β (IL-1β) when senescence was induced in HUVECs [9]
We examined whether cellular senescence occurs in the cavernous body of diabetic mice
Summary
Erectile dysfunction (ED) is a major global health concern and affects more than 10 million Japanese males [1]. It is estimated that more than 50% Japanese males who are aged >60 years suffer from ED. There are several reasons why ED frequently occurs in the elderly population. Hypogonadism occurs in the elderly population, and it has been reported that testosterone replacement therapy restores erectile function in these patients [2, 3]. PLOS ONE | DOI:10.1371/journal.pone.0124129 April 20, 2015
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