Loss of Aklotho Causes Reduced Motor Ability and Short Lifespan in Zebrafish

Abstract

The klotho gene encodes a transmembrane protein aKlotho that interacts with a fibroblast growth factor receptor in renal tubular epithelial cells and functions as a co-receptor for FGF23, which is an osteocytes-derived hormone. It is known that this bone-to-kidney signal promotes urinary phosphate excretion. Interestingly, aKlotho-deficient mice show accelerated aging and shortened life span in addition to dysregulation of serum phosphorus. However, physiological basis of aging-related function of aklotho and its generality in animals remain unclear. The aklotho-deficient vertebrate animals other than mice have been awaited as an alternative premature aging model. We here employed zebrafish in our aklotho study and revealed that aklotho mutant zebrafish appear to be normal at 3 months postfertilization (mpf) in young adults but eventually undergo premature death by 9 mpf, while normal zebrafish is known to survive for 42 months. We also assessed motor ability of zebrafish in a forced swimming assay and found that aklotho mutant zebrafish displayed reduced swimming performance before their survival declined. A recent study also reported a similar finding that aklotho-deficient zebrafish exhibited short life span and reduced spontaneous movements. Taken together, these results suggest that aKlotho mutant zebrafish show premature aging and are useful to investigate aging in vertebrates.