Abstract：
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
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 DJdoi
10.1016/j.celrep.2019.08.013subject
Has Abstractpub_date
2019-09-10 00:00:00pages
2767-2776.e5issue
11issn
2211-1247pii
S2211-1247(19)31046-0journal_volume
28pub_type
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