Klotho Expression is Induced by Calorie Restriction in Adult Male Rats

Summary The elderly population in Japan is increasing and one consequence of aging is a reduction in serum zinc levels. Zinc defi ciency reduces the mRNA expression of Klotho an anti‑aging gene which when disrupted in mice accelerates the aging process. Although aging is one of the greatest risk factors for disease development later in life adhering to a calo‑ rie‑restricted (CR diet can slow the aging rate and extend life span in many organisms. This study examined the eff ect of a CR diet on Klotho expression in the kidney of an animal model. Fourteen mature male SD rats were aged until they weighed �500 g each and were then housed in individual cages and fed a special diet consisting of 65% carbohy‑ drate 20% protein 10% fat and 0.01% zinc ����������. After 1 week the animals were separated into a control group (n=7; mean body weight 511.4 � 13.7 g in which each rat consumed 150 kcal/day and a CR group (n=7; mean body weight 529.3 � 17.2 g in which each rat consumed 60% of the control calorie intake. After 4 weeks mean body weight in the CR group was reduced by 13% compared with that in the control group. Serum zinc levels were signifi cantly lower in the CR group (109.7 � 11.3 µg/dL compared with the control (132.7 � 4.9 µg/dL. Western blot analysis revealed signifi cantly increased Klotho expression in the CR group (0.57 � 0.05 compared with the control (0.28 � 0.05. These re‑ sults suggest that Klotho expression is induced by calorie restriction and is inversely related to serum zinc levels.