Singh AP, Sosa MX, Fang J, Shanmukhappa SK, Hubaud A, Fawcett CH, Molind GJ, Tsai T, Capodieci P, Wetzel K, Sanchez E, Wang G, Coble M, Tang W, Cadena SM, Fishman MC, Glass DJ. 2019. αKlotho Regulates Age-Associated Vascular Calcification and Lifespan in Zebrafish. Cell reports. 28(11):2767-2776.e5. Pubmed: 31509740 DOI:S2211-1247(19)31046-0


The hormone αKlotho regulates lifespan in mice, as knockouts die early of what appears to be accelerated aging due to hyperphosphatemia and soft tissue calcification. In contrast, the overexpression of αKlotho increases lifespan. Given the severe mouse phenotype, we generated zebrafish mutants for αklotho as well as its binding partner fibroblast growth factor-23 (fgf23). Both mutations cause shortened lifespan in zebrafish, with abrupt onset of behavioral and degenerative physical changes at around 5 months of age. There is a calcification of vessels throughout the body, most dramatically in the outflow tract of the heart, the bulbus arteriosus (BA). This calcification is associated with an ectopic activation of osteoclast differentiation pathways. These findings suggest that the gradual loss of αKlotho found in normal aging might give rise to ectopic calcification.
Copyright © 2019 Novartis Institutes for Biomedical Research. Published by Elsevier Inc. All rights reserved.

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Photo of Mark C. Fishman

Mark C. Fishman’s group studies the heart-brain connection. They employ a range of genetic, developmental, and neurobiological tools in zebrafish to understand what the heart tells the brain, and how critical internal sensory systems adjust homeostatic and somatic behaviors, including social interactions.

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