Project name: Transcriptomic signatures of telomerase-dependent and -independent ageing, un the zebrafish gut and brain

Description: Telomerase is best known for its role in the maintenance of telomere length and its implications for ageing and cancer. The mechanisms, kinetics and tissue-specificity underlying the protective or deleterious mechanisms of telomerase, however, remain largely unknown. Here, we sought to determine the telomerase-dependent and -independent transcriptomic changes with ageing, in the gut and brain, as examples of high and low proliferative tissues, respectively. We hypothesised this could shed light on common telomerase-dependent and -independent therapeutic targets aimed at preventing or ameliorating age-associated dysfunction in both tissues. For this, we used the zebrafish model which, similarly to humans, depends on telomerase for health- and life-span. We performed whole tissue RNA sequencing of gut and brain, in naturally aged zebrafish alongside prematurely aged telomerase null mutants (tert-/-), throughout their lifespan. Our study highlights stem cell exhaustion as the first main hallmark of ageing to be de-regulated in WT zebrafish gut and brain. Towards the end of life, altered intercellular communication becomes the main hallmark of ageing de-regulated in both gut and brain, and this is accelerated in both tissues, in the absence of telomerase. Finally, we identify 7 key gene changes common between the gut and brain at the early stages of ageing, highlighting potential early intervention therapeutic targets for preventing age-associated dysfunction in both tissues.Overall design: RNA-Sequencing of whole gut and brain tissues, throughout the lifespan of WT and telomerase-deficient (tert-/-) fish. The data 4 age-groups of WT (2, 9, 22 and >30 months), corresponding to young, adult, median lifespan and old; and 3 age-groups of telomerase-deficient fish (2, 9, and 22 months), which correspond to young, medium lifespan and old. Each group has a sample size of 3 animals.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2022-06-07