TY - JOUR T1 - Transcriptomic Signatures of Telomerase-Dependent and -Independent Ageing, in the Zebrafish gut and Brain JF - bioRxiv DO - 10.1101/2022.05.24.493215 SP - 2022.05.24.493215 AU - Raquel R. Martins AU - Michael Rera AU - Catarina M. Henriques Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/05/24/2022.05.24.493215.abstract N2 - 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 lifespan. 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.Competing Interest StatementThe authors have declared no competing interest. ER -