2013 Fiscal Year Final Research Report

Impact of phosphate toxicity on skin aging

Research Project

Project/Area Number	24659527
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Single-year Grants
Research Field	Dermatology
Research Institution	Nagoya University
Principal Investigator	OGAWA Yasushi 名古屋大学, 医学部附属病院, 助教 (10567754)
Project Period (FY)	2012-04-01 – 2013-03-31
Keywords	ケラチノサイト / 老化 / リン代謝
Research Abstract	Hyperphosphatemia is caused by several diseases including chronic renal failure, and is often accompanied by skin manifestations that mimic aging. The "phosphate toxicity" hypothesis suggests that hyperphosphatemia induce aging like symptoms of the body, however, the direct consequence of the high phosphate condition on keratinocytes was not well studied. In this study we verified that normal human epidermal keratinocytes (NHEK) are driven into early cellular senescence if cultured under non-optimum phosphate condition. NHEK showed highest population doubling levels (PDL) when cultured in 4 mM phosphate and the concentration lower or higher than this level resulted in decreased PDL. The decrease in PDL was accompanied by increased expression of keratinocyte differentiation markers. No increase in senescence associated secreted proteins was observed. It may be suggested that high phosphate condition may drive NHEK to differentiated state leading to accelerated aging-like phenotype.