Abstract
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.
Highlights
Aging-related changes in the immune system occur at two stages of life
To confirm that our mice retained this feature on the C57BL/6 background, expression of secreted and membrane kl mRNAs in kidney were analyzed by qPCR (Figure 1A)
Www.aging-us.com and E) as was previously reported [24]. These results show that the effects of decreased Klotho expression on lifespan and the premature aging-related phenotypes were largely alleviated on a C57BL/6 background
Summary
Aging-related changes in the immune system occur at two stages of life. The first begins at a young age in humans and mice, when the thymus begins to involute as the thymic micro-environment deteriorates, followed by reduction in the number of developing thymocytes. The second phase of immune system decline takes place in much older humans and mice and correlates with decreased ability to fight infections [3, 4], inadequate response to vaccination [5,6,7] and decreased protection from cancer [8,9,10]. Despite thymic involution and BM changes, the peripheral immune system in adult mice remains reasonably stable until age-related decline is noted at a much older age. Mechanisms that regulate the maintenance of immune system during adult life remain to be adequately elucidated
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