Telomeres, repeated sequences at the end of chromosomes, act as a countdown with each cell division. When telomere length becomes too short, cells become senescent or undergo self-destruct, thanks to the activity of TP53. This study delves into the interplay between telomerase, TP53, and telomere length by disrupting these mechanisms and observing the outcomes.
Telomerase activity is limited in humans, leading to telomere attrition and aging in various tissues. Short telomeres trigger DNA damage responses and activate p53, resulting in cell senescence or apoptosis. Zebrafish, which also have restricted telomerase expression, exhibit premature aging due to early telomere shortening and subsequent tissue disruption.
Mutant zebrafish lacking telomerase display premature aging phenotypes, such as impaired cell proliferation, DNA damage accumulation, and disrupted tissue homeostasis. Interestingly, mutation of tp53 in these telomerase-deficient zebrafish extends male fertility and lifespan, indicating a genetic interdependence between tp53 and telomerase function.
The study also reveals that loss of telomerase extends the lifespan of tp53 mutants, while reducing cancer incidence in double mutants. This reciprocal relationship between tp53 and telomerase highlights a complex interplay that affects lifespan and cancer susceptibility in zebrafish models.
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