Abstract

The Naked Mole Rat (NMR), Heterocephalus glaber, provides an interesting model for studying biomarkers of longevity due to its long lifespan of more than 30 years, almost ten times longer than that of mice and rats. α-Klotho (klotho) is an aging-suppressor gene, and overexpression of klotho is associated with extended lifespan in mice. Klotho is predominantly expressed in the kidney. The expression profile of klotho in the NMR has not previously been reported. The present investigation studied the expression of klotho in the kidney of NMR with that of Rattus Norvegicus (RN) and demonstrated that klotho was expressed in the kidney of NMR at the same level as found in RN. Besides, a significant expression of Kl mRNA was found in the liver of NMR, in contrast to RN, where no hepatic expression was detected. The Klotho expression was further confirmed at the protein level. Thus, the results of the present comparative study indicate a differential tissue expression of klotho between different species. Besides its important function in the kidney, Klotho might also be of significance in the liver of NMR. It is suggested that the hepatic extrarenal expression of klotho may function as a further longevity-related factor in supplement to the Klotho in the kidney.

Highlights

  • The Naked Mole Rat (NMR), Heterocephalus glaber, provides an interesting model for studying biomarkers of longevity due to its long lifespan of more than 30 years, almost ten times longer than that of mice and rats. α-Klotho is an aging-suppressor gene, and overexpression of klotho is associated with extended lifespan in mice

  • The expression profile of klotho in NMR tissues was examined by designing specific primers for amplification of membrane-bound α-klotho (mKl) and reference genes, as the NMR rats do not share the same sequence as Rattus Norvegicus (RN) (Table 2)

  • This was initiated by examining the kidney tissue, as the kidney previously has been shown to be the primary source of klotho expression in mammals. Quantitative Polymerase chain reaction (PCR) (qPCR) analyses were performed on kidney tissues of NMR from both the zoo (Randers Regnskov, Denmark) and the research colony population (Gorbunova and Seluanov laboratory)

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Summary

Introduction

The Naked Mole Rat (NMR), Heterocephalus glaber, provides an interesting model for studying biomarkers of longevity due to its long lifespan of more than 30 years, almost ten times longer than that of mice and rats. α-Klotho (klotho) is an aging-suppressor gene, and overexpression of klotho is associated with extended lifespan in mice. The Naked Mole Rat (NMR), Heterocephalus glaber, provides an interesting model for studying biomarkers of longevity due to its long lifespan of more than 30 years, almost ten times longer than that of mice and rats. The NMR is a mouse-sized (approximately 35 g in weight) rodent, which does not show any increase in the age-specific hazard of mortality, in defiance of Gompertzian l­aws[5] This species shows no decrease in physiological capacity, cardio-vascular function, gastrointestinal function, glucose tolerance, and reproductive capacity until the third decades of l­ife[6,7]. Α-Klotho (in the following called Klotho) is an evolutionarily, highly conserved kidney hormone, that is related to ­longevity[13,14] It is distinctly expressed in the kidney and found in small amounts in the parathyroid glands and the plexus choroideus in the ­brain[13,15]. The klotho deficient mice develop accelerated aging features besides shortened regionh.dk

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