α-klotho overexpression and age-related changes in mouse lenses across lifespan

Abstract

Purpose : Klotho is a transmembrane proteins implicated in aging-related phenotypes (in brain, kidney, cardiovascular system, organism longevity) in humans and experimental animals. Klotho has been shown to be protective during aging and overexpression of it has been demonstrated to be neuroprotective in the brain. The klotho family of genes includes α-klotho, β-klotho and γ-klotho. α-klotho is expressed in the lens and the brain. However it is not known how α-klotho affects aging of the lens. Here we investigated the effect of α-klotho overexpression in the lens across the mouse lifespan.

Methods : α-klotho overexpressing transgenic and littermate non-trangenic mice were bred, maintained and genotyped at Boston University. Male and female mice were sacrificed at selected ages across the lifespan. Lenses were isolated and imaged under with a custom-adapted Zeiss stereophotomicroscope and digital Nikon camera.

Results : Aged mice displayed age-related cortical opacities. There was no overt different phenotype between the normal α-klotho expressing non-transgenic mice and the transgenic α-klotho overexpressing mice. In contrast to previously reported studies in the brain, overexpression of α-klotho did not appear to have any gross effect on aging lens phenotype.

Conclusions : Aged mice displayed age-related cortical opacities. There was no overt different phenotype between the normal α-klotho expressing non-transgenic mice and the transgenic α-klotho overexpressing mice. Further studies using α-klotho knock-out mice may provide further insight into the role of α-klotho in lens aging as has been reported for other tissues.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.