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TRANSCRIPTOMIC SIGNATURES OF TELOMERASE-DEPENDENT AND -INDEPENDENT AGEING, IN THE ZEBRAFISH GUT AND BRAIN

Raquel R. Martins, View ORCID ProfileMichael Rera, View ORCID ProfileCatarina M. Henriques
doi: https://doi.org/10.1101/2022.05.24.493215
Raquel R. Martins
1The Bateson Centre, Healthy Lifespan Institute and Department of Oncology and Metabolism, University of Sheffield Medical School, Sheffield, UK
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Michael Rera
2Université de Paris / Inserm- Centre de Recherche Interdisciplinaire (CRI Paris)
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Catarina M. Henriques
1The Bateson Centre, Healthy Lifespan Institute and Department of Oncology and Metabolism, University of Sheffield Medical School, Sheffield, UK
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  • For correspondence: c.m.henriques@sheffield.ac.uk
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SUMMARY

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 Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 26, 2022.
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TRANSCRIPTOMIC SIGNATURES OF TELOMERASE-DEPENDENT AND -INDEPENDENT AGEING, IN THE ZEBRAFISH GUT AND BRAIN
Raquel R. Martins, Michael Rera, Catarina M. Henriques
bioRxiv 2022.05.24.493215; doi: https://doi.org/10.1101/2022.05.24.493215
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TRANSCRIPTOMIC SIGNATURES OF TELOMERASE-DEPENDENT AND -INDEPENDENT AGEING, IN THE ZEBRAFISH GUT AND BRAIN
Raquel R. Martins, Michael Rera, Catarina M. Henriques
bioRxiv 2022.05.24.493215; doi: https://doi.org/10.1101/2022.05.24.493215

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