Telomerase Is Required for Zebrafish Lifespan

• DOI: 10.1371/journal.pgen.1003214
• Publication Date: 2013-01-17T16:49:14Z
• Authors: Catarina M. Henri...; Madalena C. Carneiro; Inês M. Tenente; António Jacinto; Miguel Godinho Fe...
• Keywords: 0301 basic medicine; Aging; Apoptosis; QH426-470; Telomere; Cell Line; Gene Knockout Techniques; 03 medical and health sciences; Gene Expression Regulation; Genetics; Animals; Humans; Tumor Suppressor Protein p53; Telomerase; Cellular Senescence; Telomere Shortening; Zebrafish; Research Article; Cell Proliferation; DNA Damage

Telomerase activity is restricted in humans. Consequentially, telomeres shorten most cells throughout our lives. Telomere dysfunction vertebrates has been primarily studied inbred mice strains with very long that fail to deplete telomeric repeats during their lifetime. It is, therefore, unclear how telomere shortening regulates tissue homeostasis naturally short telomeres. Zebrafish have telomerase expression and human-like length. Here we show first-generation tert−/− zebrafish die prematurely shorter fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, sarcopaenia. mutants impaired cell proliferation, accumulation of DNA damage markers, a p53 response leading early apoptosis, followed by senescent cells. Apoptosis observed the proliferative niche germ Cell but not rescued tp53−/−tert−/− mutants, underscoring as mediator deficiency consequent instability. Thus, limiting for lifespan, enabling study ageing individuals.