Impact of phosphate toxicity on skin aging

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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.