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

Article (PDF Available)inNature Communications 2(1):384 · July 2011with12 Reads
DOI: 10.1038/ncomms1389 · Source: PubMed
Abstract
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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    • "This process involves the reversion of certain epigenetic modifications [246,247], but whether dedifferentiation is able to revert aged adult tissues to a youthful status is unknown. In this connection, it is worth noting that newt lens regeneration, an age-resistant process, takes place by transdifferentiation of somatic cells [51]. Interestingly, it has been observed that this process involves a step of dedifferentiation and expression of pluripotency genes such as Sox2, c-myc and Klf4 [248], and this could represent a reversion of age status. "
    [Show abstract] [Hide abstract] ABSTRACT: Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.
    Full-text · Article · Oct 2015
    • "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). "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Jun 2015
    • "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). "
    [Show abstract] [Hide abstract] 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.
    Full-text · Article · Jun 2015
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