糖化ストレスによる腎臓病と腎臓の老化

Summary 　Advanced glycation endproducts （AGEs） and their precursors （reactive carbonyl compounds） are mainly filtrated and metabolized in kidney. They accumulate in damaged kidney and contribute to the disease progression. Further, AGE accumulation is also significantly increased in kidney with aging, suggesting that glycative stress contributes to the aging process. We have recently demonstrated that the activity of AGE precursor detoxifying enzyme （glyoxalase I） in the kidney is significantly decreased with age in rats and that decreasing AGE formation by glyoxalase I overexpression ameliorates renal phenotypes with aging. In particular, aged （14-month-old） rats overexpressing glyoxalase I show decreased renal senescence phenotypic changes as compared to age-matched wild-type rats, without any metabolic disorders: amelioration of age-related interstitial thickening with renal dysfunction, and a decrease in senescence marker （senescence associated beta-gal, SABG）-positive tubules. AGEs thus play a role in senescence and glyoxalase I plays a pivotal role in the amelioration of renal senescence via, at least in part, the inhibition of AGE formation.