The Progression of Aging in Klotho Mutant Mice Can Be Modified by Dietary Phosphorus and Zinc

Abstract

Reduction in klotho gene expression causes accelerated senescence in klotho mutant mice. We have now found two key substances, phosphorus and zinc, which affect the appearance of klotho phenotypes. Klotho mutant homozygotes fed nonpurified diet with a phosphorus concentration of 1.03 g/100 g showed typical klotho phenotypes. However, most of the klotho phenotypes no longer appeared in male homozygotes fed a 0.4 g/100 g phosphorus diet. These homozygotes were capable of spermatogenesis. In the kidneys of the rescued male homozygotes, klotho protein expression was clearly detected. On the other hand, female klotho mice required supplementation of 0.25 g/100 g zinc orotate to the 0.4 g/100 g phosphorus diet to be rescued. Unlike in the rescued male mice, klotho protein levels in the kidneys of the rescued females were quite low. Wild-type (C3H/He) mice fed 1.5 or 1.0 g/100 g phosphorus diets had lower klotho protein expression in the kidneys than those fed a 0.4 g/100 g phosphorus diet (Kruskal-Wallis test, P < 0.05). These results indicate that dietary phosphorus and zinc modulate the phenotypes of klotho mice, and that klotho expression in the kidneys is regulated not only in klotho mutant mice, but also in wild-type mice.

Klotho Up-regulates Renal Calcium Channel Transient Receptor Potential Vanilloid 5 (TRPV5) by Intra- and Extracellular N-glycosylation-dependent Mechanisms

“…Electrophysiological Recording-Approximately 48 h after transfection, cells were dissociated and placed in a chamber for ruptured whole-cell recordings as described previously (24). Transfected cells were identified for recording by green fluorescence.…”

“…Mice with homozygous knockout of fgf23 have profound hyperphosphatemia and the same premature aging phenotypes as homozygous kl hypomorphic mice (23). Dietary phosphate restriction rescues premature aging and death in both fgf23 knockout and kl hypomorphic mice (24,25).…”

Effects of the Sri Lankan medicinal plant, Salacia reticulata, in rheumatoid arthritis

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Effects of Dietary Phosphate on Ectopic Calcification and Muscle Function in mdx Mice

“…Klotho mutant mice also exhibit multiple age-associated disorders, such as arteriosclerosis, osteoporosis, short-life span, and ectopic calcification. However, as these phenotypes are rescued by the restriction of dietary phosphorus alone in male Klotho mice (Morishita et al, 2010) we predicted that the amount of dietary Pi intake influences the precipitation of calcium in mdx mice, and that the restriction of dietary Pi may improve mdx muscle pathology and function.…”