Regenerative capacity in newts is not altered by repeated regeneration and ageing

National Institute for Basic Biology, National Institutes of Natural Sciences, Nishigonaka 38, Myodaiji, Okazaki, Aichi 444-8585, Japan.
Nature Communications (Impact Factor: 11.47). 07/2011; 2(1):384. DOI: 10.1038/ncomms1389
Source: PubMed


The extent to which adult newts retain regenerative capability remains one of the greatest unanswered questions in the regeneration field. Here we report a long-term lens regeneration project spanning 16 years that was undertaken to address this question. Over that time, the lens was removed 18 times from the same animals, and by the time of the last tissue collection, specimens were at least 30 years old. Regenerated lens tissues number 18 and number 17, from the last and the second to the last extraction, respectively, were analysed structurally and in terms of gene expression. Both exhibited structural properties identical to lenses from younger animals that had never experienced lens regeneration. Expression of mRNAs encoding key lens structural proteins or transcription factors was very similar to that of controls. Thus, contrary to the belief that regeneration becomes less efficient with time or repetition, repeated regeneration, even at old age, does not alter newt regenerative capacity.

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    • "In fact, there are several reports with opposing results. In newts, for example, the entire eye lens can regenerate and neither repeated regeneration nor old age altered the regenerative capacity of the lens (Eguchi et al., 2011). In zebrafish, two studies reported that old animals show impaired fin regeneration and that the time to regenerate 50% of the fin increased with advanced age (Tsai et al., 2007; Anchelin et al., 2011). "
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    ABSTRACT: The potential to regenerate declines with age in a wide range of organisms. A popular model system to study the mechanisms of regeneration is the fin of teleost fish, which has the ability to fully regrow upon amputation. Here, we used the short-lived killifish Nothobranchius furzeri to analyse the impact of aging on fin regeneration in more detail. We observed that young fish were able to nearly completely (98%) regenerate their amputated caudal fins within 4 weeks, whereas middle-aged fish reached 78%, old fish 57% and very old fish 46% of their original fin size. The difference in growth rate between young and old fish was already significant at 3 days post amputation (dpa) and increased with time. We therefore hypothesized that early events are crucial for the age-related differences in regenerative capacity. Indeed, we could observe a higher percentage of proliferating cells in early regenerating fin tissue of young fish compared with aged fish and larger fractions of apoptotic cells in aged fish. Furthermore, young fish showed peak upregulation of several genes involved in fgf and wnt/β-catenin signalling at an earlier time point than old fish. Our findings suggest that regenerative processes are initiated earlier and that regeneration overall is more efficient in younger fish. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
    Aging cell 06/2015; 14(5). DOI:10.1111/acel.12367 · 6.34 Impact Factor
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    • "These patterns suggest that regenerative ability is associated with age-related changes in cells that form tissues and organs, as well as maturation of systems that broadly regulate development and physiology (Seifert and Voss, 2013). Exceptions include lens regeneration in adult newts (Eguchi et al., 2011) and fin regeneration in zebrafish (Itou et al., 2012). "
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    ABSTRACT: Mexican axolotls lose potential for lens regeneration two weeks after hatching. We used microarrays to identify differently expressed genes before and after this critical time, using RNA isolated from iris. Over 3700 genes were identified as differentially expressed in response to lentectomy between young (seven days post hatching) and old (three-months post hatching) axolotl larvae. Strikingly, many of the genes were only expressed in the early or late iris. Genes that were highly expressed in young iris significantly enriched electron transport chain, transcription, metabolism, and cell cycle gene ontologies, all of which are associated with lens regeneration. In contrast, genes associated with cellular differentiation and tissue maturation were uniquely expressed in old iris. Many of these expression differences strongly suggest that young and old iris samples were collected before and after the spleen became developmentally competent to produce and secrete cells with humoral and innate immunity functions. Our study establishes the axolotl as a powerful model to investigate age-related cellular differentiation and immune system ontogeny within the context of tissue regeneration.This article is protected by copyright. All rights reserved.
    06/2014; 1(3). DOI:10.1002/reg2.25
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    • "Normally developed out of the epidermis at the embryonic stage, the lens re-emerges in a stepwise fashion from the edge of the iris instead (Henry and Tsonis 2010). Neither age nor repeated amputation seems to diminish this regenerative capability (Eguchi et al. 2011). But it turns out that an injection of the growth factor, FGF2, is all it takes to trigger the onset of development (Hayashi et al. 2004), along with the subsequent expression of other genes. "
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    ABSTRACT: In developmental and evolutionary biology, particular emphasis has been given to the relationship between transcription factors and the cognate cis-regulatory elements of their target genes. These constitute the gene regulatory networks that control expression and are assumed to causally determine the formation of structures and body plans. Comparative analysis has, however, established a broad sequence homology among species that nonetheless display quite different anatomies. Transgenic experiments have also confirmed that many developmentally important elements are, in fact, functionally interchangeable. Although dependent upon the appropriate degree of gene expression, the actual construction of specific structures appears not directly linked to the functions of gene products alone. Instead, the self-formation of complex patterns, due in large part to epigenetic and non-genetic determinants, remains a persisting theme in the study of ontogeny and regenerative medicine. Recent evidence indeed points to the existence of a self-organizing process, operating through a set of intrinsic rules and forces, which imposes coordination and a holistic order upon cells and tissue. This has been repeatedly demonstrated in experiments on regeneration as well as in the autonomous formation of structures in vitro. The process cannot be wholly attributed to the functional outcome of protein-protein interactions or to concentration gradients of diffusible chemicals. This phenomenon is examined here along with some of the methodological and theoretical approaches that are now used in understanding the causal basis for self-organization in development and its evolution.
    Theory in Biosciences 04/2014; 133(3-4). DOI:10.1007/s12064-014-0200-4 · 1.23 Impact Factor
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