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The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing
Improvements in hygiene and health management have driven significant increases in human lifespan over the last 50 years. Frustratingly however, this extension of lifespan has not been matched by equivalent improvements in late-life health, not least due to the global pandemic in type-2 diabetes, ob...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108737/ https://www.ncbi.nlm.nih.gov/pubmed/32163524 http://dx.doi.org/10.1371/journal.ppat.1008391 |
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author | Crowe, Jenny Lumb, Felicity E. Doonan, James Broussard, Margaux Tarafdar, Anuradha Pineda, Miguel A. Landabaso, Carmen Mulvey, Lorna Hoskisson, Paul A. Babayan, Simon A. Selman, Colin Harnett, William Harnett, Margaret M. |
author_facet | Crowe, Jenny Lumb, Felicity E. Doonan, James Broussard, Margaux Tarafdar, Anuradha Pineda, Miguel A. Landabaso, Carmen Mulvey, Lorna Hoskisson, Paul A. Babayan, Simon A. Selman, Colin Harnett, William Harnett, Margaret M. |
author_sort | Crowe, Jenny |
collection | PubMed |
description | Improvements in hygiene and health management have driven significant increases in human lifespan over the last 50 years. Frustratingly however, this extension of lifespan has not been matched by equivalent improvements in late-life health, not least due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, all ageing-associated conditions exacerbated and accelerated by widespread adoption of the high calorie Western diet (HCD). Recently, evidence has begun to emerge that parasitic worm infection might protect against such ageing-associated co-morbidities, as a serendipitous side-effect of their evolution of pro-survival, anti-inflammatory mechanisms. As a novel therapeutic strategy, we have therefore investigated the potential of ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, to improve healthspan (the period of life before diseases of ageing appear) by targeting the chronic inflammation that drives metabolic dysregulation underpinning ageing-induced ill-health. We administered ES-62 subcutaneously (at a dose of 1 μg/week) to C57BL/6J mice undergoing HCD-accelerated ageing throughout their lifespan, while subjecting the animals to analysis of 120 immunometabolic responses at various time-points. ES-62 improved a number of inflammatory parameters, but markedly, a range of pathophysiological, metabolic and microbiome parameters of ageing were also successfully targeted. Notably, ES-62-mediated promotion of healthspan in male and female HCD-mice was associated with different mechanisms and reflecting this, machine learning modelling identified sex-specific signatures predictive of ES-62 action against HCD-accelerated ageing. Remarkably, ES-62 substantially increased the median survival of male HCD-mice. This was not the case with female animals and unexpectedly, this difference between the two sexes could not be explained in terms of suppression of the chronic inflammation driving ageing, as ES-62 tended to be more effective in reducing this in female mice. Rather, the difference appeared to be associated with ES-62’s additional ability to preferentially promote a healthier gut-metabolic tissue axis in male animals. |
format | Online Article Text |
id | pubmed-7108737 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71087372020-04-03 The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing Crowe, Jenny Lumb, Felicity E. Doonan, James Broussard, Margaux Tarafdar, Anuradha Pineda, Miguel A. Landabaso, Carmen Mulvey, Lorna Hoskisson, Paul A. Babayan, Simon A. Selman, Colin Harnett, William Harnett, Margaret M. PLoS Pathog Research Article Improvements in hygiene and health management have driven significant increases in human lifespan over the last 50 years. Frustratingly however, this extension of lifespan has not been matched by equivalent improvements in late-life health, not least due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, all ageing-associated conditions exacerbated and accelerated by widespread adoption of the high calorie Western diet (HCD). Recently, evidence has begun to emerge that parasitic worm infection might protect against such ageing-associated co-morbidities, as a serendipitous side-effect of their evolution of pro-survival, anti-inflammatory mechanisms. As a novel therapeutic strategy, we have therefore investigated the potential of ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, to improve healthspan (the period of life before diseases of ageing appear) by targeting the chronic inflammation that drives metabolic dysregulation underpinning ageing-induced ill-health. We administered ES-62 subcutaneously (at a dose of 1 μg/week) to C57BL/6J mice undergoing HCD-accelerated ageing throughout their lifespan, while subjecting the animals to analysis of 120 immunometabolic responses at various time-points. ES-62 improved a number of inflammatory parameters, but markedly, a range of pathophysiological, metabolic and microbiome parameters of ageing were also successfully targeted. Notably, ES-62-mediated promotion of healthspan in male and female HCD-mice was associated with different mechanisms and reflecting this, machine learning modelling identified sex-specific signatures predictive of ES-62 action against HCD-accelerated ageing. Remarkably, ES-62 substantially increased the median survival of male HCD-mice. This was not the case with female animals and unexpectedly, this difference between the two sexes could not be explained in terms of suppression of the chronic inflammation driving ageing, as ES-62 tended to be more effective in reducing this in female mice. Rather, the difference appeared to be associated with ES-62’s additional ability to preferentially promote a healthier gut-metabolic tissue axis in male animals. Public Library of Science 2020-03-12 /pmc/articles/PMC7108737/ /pubmed/32163524 http://dx.doi.org/10.1371/journal.ppat.1008391 Text en © 2020 Crowe et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Crowe, Jenny Lumb, Felicity E. Doonan, James Broussard, Margaux Tarafdar, Anuradha Pineda, Miguel A. Landabaso, Carmen Mulvey, Lorna Hoskisson, Paul A. Babayan, Simon A. Selman, Colin Harnett, William Harnett, Margaret M. The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing |
title | The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing |
title_full | The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing |
title_fullStr | The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing |
title_full_unstemmed | The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing |
title_short | The parasitic worm product ES-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing |
title_sort | parasitic worm product es-62 promotes health- and life-span in a high calorie diet-accelerated mouse model of ageing |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108737/ https://www.ncbi.nlm.nih.gov/pubmed/32163524 http://dx.doi.org/10.1371/journal.ppat.1008391 |
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