Negligible senescence in naked mole rats may be a consequence of well-maintained splicing regulation
dc.contributor.author | Lee, BP | |
dc.contributor.author | Smith, M | |
dc.contributor.author | Buffenstein, R | |
dc.contributor.author | Harries, LW | |
dc.date.accessioned | 2020-04-21T10:18:05Z | |
dc.date.issued | 2020-01-11 | |
dc.description.abstract | Naked mole-rats (NMRs) have amongst the longest lifespans relative to body size of any known, non-volant mammalian species. They also display an enhanced stress resistance phenotype, negligible senescence and very rarely are they burdened with chronic age-related diseases. Alternative splicing (AS) dysregulation is emerging as a potential driver of senescence and ageing. We hypothesised that the expression of splicing factors, important regulators of patterns of AS, may differ in NMRs when compared to other species with relatively shorter lifespans. We designed assays specific to NMR splicing regulatory factors and also to a panel of pre-selected brain-expressed genes known to demonstrate senescence-related alterations in AS in other species, and measured age-related changes in the transcript expression levels of these using embryonic and neonatal developmental stages through to extreme old age in NMR brain samples. We also compared splicing factor expression in both young mouse and NMR spleen and brain samples. Both NMR tissues showed approximately double the expression levels observed in tissues from similarly sized mice. Furthermore, contrary to observations in other species, following a brief period of labile expression in early life stages, adult NMR splicing factors and patterns of AS for functionally relevant brain genes remained remarkably stable for at least two decades. These findings are consistent with a model whereby the conservation of splicing regulation and stable patterns of AS may contribute to better molecular stress responses and the avoidance of senescence in NMRs, contributing to their exceptional lifespan and prolonged healthspan. | en_GB |
dc.description.sponsorship | Calico Life Sciences LLC | en_GB |
dc.identifier.citation | Published online 11 January 2020 | en_GB |
dc.identifier.doi | 10.1007/s11357-019-00150-7 | |
dc.identifier.uri | http://hdl.handle.net/10871/120753 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature / American Aging Association (AGE) | en_GB |
dc.rights | © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.title | Negligible senescence in naked mole rats may be a consequence of well-maintained splicing regulation | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-04-21T10:18:05Z | |
dc.identifier.issn | 2509-2715 | |
dc.description | This is the final version. Available on open access from Springer Nature via the DOI in this record | en_GB |
dc.identifier.journal | GeroScience | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-12-27 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-01-11 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-04-21T10:11:43Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-04-21T10:18:08Z | |
refterms.panel | A | en_GB |
refterms.depositException | publishedGoldOA |
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