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Abstract: PO0325

Extrarenal Expression of the Kidney-Related Longevity Gene, α-Klotho, in the Long-Living Naked Mole Rat (Heterocephalus glaber): A Comparative Biology Study

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Morevati, Marya, Rigshospitalet, Kobenhavn, Denmark
  • Egstrand, Søren, Rigshospitalet, Kobenhavn, Denmark
  • Nordholm, Anders, Rigshospitalet, Kobenhavn, Denmark
  • Mace, Maria Lerche, Rigshospitalet, Kobenhavn, Denmark
  • Olgaard, Klaus, Rigshospitalet, Kobenhavn, Denmark
  • Lewin, Ewa, Rigshospitalet, Kobenhavn, Denmark
Background

The naked mole-rat (NMR) is expanding in popularity as a model for studying biomarkers of aging and mineral metabolism. NMR has a lifespan of 30 years, almost ten times longer than the mouse and rat (app. 3-4 years).
α-klotho (Kl) is an aging-suppressor gene. Knockout of Kl is associated with decreased lifespan, and overexpression of this gene is linked to extended lifespan in mice. Kl is predominantly expressed in the kidney. We speculated that the expression level of this gene might play a role in the longevity of NMR. The present comparative study aimed to establish the expression level of Kl in long-living NMR vs. normal rats, Rattus norvegicus (RN).

Methods

Ten NMR, kindly provided by Randers Regnskov (Danish Zoo) (N=5) and Gorbunova and Seluanov laboratory (Aging Research Center, University of Rochester, USA) (N=5) were used and compared to corresponding tissues from RN (N=9). Methods used were: QPCR, standard PCR, and Sanger sequencing.

Results

In the kidney, similar levels of Kl mRNA were observed between those two species by qPCR (RN: 0.9± 0.1 vs. NMR: 1.2± 0.2; n.s.). The expression of Kl was further examined in the lung, skin, and liver of NMR, compared to RN. There was no expression of Kl in the lung and skin of NMR.
In the liver of NMR, a high expression of Kl mRNA was observed (Cp: 25) by qPCR in contrast to RN, where no expression was detected. Sanger sequencing was performed to confirm that the gene expressed in the liver was Kl. In order to ensure that this was not a truncated form of Kl, which could be a target for mRNA decay, the predicted region for alternative splicing sites for Kl was sequenced in NMR. These results indicated that this was not the case, neither in the kidney nor in the liver.

Conclusion

This comparative study showed for the first time that α-klotho is significantly expressed in the liver of NMR, while the gene is absent in the liver of RN. The expression levels of α-klotho were similar in kidneys of NMR and RN. Further experimental work is required to clarify whether the hepatic expression of α-klotho might contribute to the longevity of the NMR.

Funding

  • Government Support - Non-U.S.