Parasitic worm-derived ES-62 promotes health- and life-span in high calorie diet-fed mice
Crowe, J.; Lumb, F. E.; Doonan, J.; Broussard, M.; Tarafdar, A.; Pineda, M. A.; Landabaso, C.; Mulvey, L.; Hoskisson, P. A.; Babayan, S.; Selman, C.; Harnett, W.; Harnett, M. M.
Show abstract
The recent extension of human lifespan has not been matched by equivalent improvements in late-life health due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, ageing-associated conditions exacerbated by widespread adoption of the high calorie Western diet (HCD). As a novel therapeutic strategy, we have investigated the potential of ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, to improve healthspan by targeting the chronic inflammation that drives metabolic dysregulation underpinning ageing-induced ill-health. We found that ES-62 improves a range of inflammatory but also pathophysiological, metabolic and microbiome parameters, when administered subcutaneously at only 1 {micro}g/week throughout the lifespan of HCD-fed mice. Strikingly, ES-62 induced sex-specific healthspan signatures and indeed, it substantially increased the median survival of male, but not female, HCD-mice. Modelling of 113 responses contributing to these differential signatures by machine learning approaches now signposts candidate parameters key to promoting both healthspan and lifespan.
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