In another study, Cai et al. showed that pair-fed mice on a calorie-restricted H-AGEs diet developed high levels of 8-isoprostanes, AGEs, AGER-1, and p66shc, coupled with low AGER-1 and glutathione/oxidized glutathione ratio, IR, marked myocardial and renal fibrosis, and shortened lifespan, compared with those on a calorie-restricted diet alone. This evidence concerns the gene DDOST and renal fibrosis.