Telomere elongation in the gut extends zebrafish lifespan

Maï, Mounir El; Guigonis, Jean-Marie; Pourcher, Thierry; Kang, Da Som; Ferreira, Miguel Godinho

doi:10.1101/2022.01.10.475664

Cited by 2 publications

(1 citation statement)

References 65 publications

(119 reference statements)

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“…Processes such as de novo formation of stem cells and the subsequent increase in average telomere length in the metamorphic gut support the idea that metamorphosis can act as a rejuvenating process in some tissues. Indeed, the gut is a central organ in ageing and the length of its telomeres has been shown to have systemic effects, including on lifespan [52]. The tissue-specific expression of mechanisms that buffer damage on telomeres (e.g.…”

Section: Discussionmentioning

confidence: 99%

Ageing across the great divide: tissue transformation, organismal growth and temperature shape telomere dynamics through the metamorphic transition

et al. 2023

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Telomere attrition is considered a useful indicator of cellular and whole-organism ageing rate. While approximately 80% of animal species undergo metamorphosis that includes extensive tissue transformations (involving cell division, apoptosis, de-differentiation and de novo formation of stem cells), the effect on telomere dynamics is unknown. We measured telomeres in Xenopus laevis developing from larvae to adults under contrasting environmental temperatures . Telomere dynamics were linked to the degree of tissue transformation during development. Average telomere length in gut tissue increased dramatically during metamorphosis, when the gut shortens by 75% and epithelial cells de-differentiate into stem cells. In the liver (retained from larva) and hindlimb muscle (newly formed before metamorphosis), telomeres gradually shortened until adulthood, likely due to extensive cell division. Tail muscle telomere lengths were constant until tail resorption, and those in heart (retained from larva) showed no change over time. Telomere lengths negatively correlated with larval growth, but for a given growth rate, telomeres were shorter in cooler conditions, suggesting that growing in the cold is more costly. Telomere lengths were not related to post-metamorphic growth rate. Further research is now needed to understand whether telomere dynamics are a good indicator of ageing rate in species undergoing metamorphosis.

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Section: Discussionmentioning

confidence: 99%

Ageing across the great divide: tissue transformation, organismal growth and temperature shape telomere dynamics through the metamorphic transition

et al. 2023

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A subset of gut leukocytes has telomerase-dependent “hyper-long” telomeres and require telomerase for function in zebrafish

et al. 2022

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Background Telomerase, the enzyme capable of elongating telomeres, is usually restricted in human somatic cells, which contributes to progressive telomere shortening with cell-division and ageing. T and B-cells cells are somatic cells that can break this rule and can modulate telomerase expression in a homeostatic manner. Whereas it seems intuitive that an immune cell type that depends on regular proliferation outbursts for function may have evolved to modulate telomerase expression it is less obvious why others may also do so, as has been suggested for macrophages and neutrophils in some chronic inflammation disease settings. The gut has been highlighted as a key modulator of systemic ageing and is a key tissue where inflammation must be carefully controlled to prevent dysfunction. How telomerase may play a role in innate immune subtypes in the context of natural ageing in the gut, however, remains to be determined. Results Using the zebrafish model, we show that subsets of gut immune cells have telomerase-dependent”hyper-long” telomeres, which we identified as being predominantly macrophages and dendritics (mpeg1.1+ and cd45+mhcII+). Notably, mpeg1.1+ macrophages have much longer telomeres in the gut than in their haematopoietic tissue of origin, suggesting that there is modulation of telomerase in these cells, in the gut. Moreover, we show that a subset of gut mpeg1.1+ cells express telomerase (tert) in young WT zebrafish, but that the relative proportion of these cells decreases with ageing. Importantly, this is accompanied by telomere shortening and DNA damage responses with ageing and a telomerase-dependent decrease in expression of autophagy and immune activation markers. Finally, these telomerase-dependent molecular alterations are accompanied by impaired phagocytosis of E. coli and increased gut permeability in vivo. Conclusions Our data show that limiting levels of telomerase lead to alterations in gut immunity, impacting on the ability to clear pathogens in vivo. These are accompanied by increased gut permeability, which, together, are likely contributors to local and systemic tissue degeneration and increased susceptibility to infection with ageing. Graphical Abstract

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Telomere elongation in the gut extends zebrafish lifespan

Cited by 2 publications

References 65 publications

Ageing across the great divide: tissue transformation, organismal growth and temperature shape telomere dynamics through the metamorphic transition

Ageing across the great divide: tissue transformation, organismal growth and temperature shape telomere dynamics through the metamorphic transition

A subset of gut leukocytes has telomerase-dependent “hyper-long” telomeres and require telomerase for function in zebrafish

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