Research Paper Volume 11, Issue 14 pp 5246—5257
Immune system development and age-dependent maintenance in Klotho-hypomorphic mice
- 1 National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
- 2 Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- 3 Current address: Department of Immunology and Microbiology, University of California San Francisco, San Francisco, CA 94143, USA
- 4 Current address: Department of Chemical Engineering, Virginia Tech, Blacksburg, VA 24061, USA
received: June 12, 2019 ; accepted: July 20, 2019 ; published: July 28, 2019 ;https://doi.org/10.18632/aging.102121
How to Cite
Copyright © 2019 Zhu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Circulating Klotho peptide hormone has anti-aging activity and affects tissue maintenance. Hypomorphic mutant Klotho [kl/kl] mice on C57BL/6xC3H, BALB/c and 129 genetic backgrounds, show decreased Klotho expression that correlate with accelerated aging including pre-mature death due to abnormally high levels of serum vitamin D. These mice also show multiple impairments in the immune system. However, it remains unresolved if the defects in the immune system stem from decreased Klotho expression or high vitamin D levels in the serum. Transfer of the kl/kl allele to pure C57BL/6 genetic background [B6-kl/kl] significantly reduced expression of Klotho at all ages. Surprisingly, B6-kl/kl mice showed normalized serum vitamin D levels, amelioration of severe aging-related phenotypes and normal lifespan. This paper reports a detailed analysis of the immune system in B6-kl/kl mice in the absence of detrimental levels of serum vitamin D. Remarkably, the data reveal that in the absence of overt systemic stress, such as abnormally high vitamin D levels, reduced expression of Klotho does not have a major effect on the generation and maintenance of the immune system.