The recent extension of human lifespan has not been matched by equivalent improvements in late-life health due to the corresponding increase in ageingassociated comorbidities and obesity, conditions exacerbated by the widespread adoption of the high calorie Western diet (HCD). Chronic low-grade inflammation underpins ageing-induced ill-health and thus we have focused on ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae that we have previously shown to have potent anti-inflammatory properties, as a novel therapeutic strategy. ES-62 was tested in a mouse model of HCD-accelerated ageing and found to ameliorate pathophysiological, inflammatory and metabolic parameters, when administered at only 1 µg/week. Strikingly, ES-62 also substantially increased the median survival of male HCD-mice. This extension was not observed with female mice and indeed, ES-62 treatment resulted in distinct gender-specific healthspan signatures. Combined with a machine learning approach, such signatures signpost candidate parameters key to promoting both healthspan and lifespan.Adoption of the modern Western diet (high fat and high sugar) has significantly contributed to a global pandemic in metabolic syndrome, obesity, type-2 diabetes and cardiovascular disease; ageing-associated conditions that impact on both wellbeing (healthspan) and lifespan 1,2 . This increasing major public health problem reflects, at least in part, that such a high calorie diet (HCD) disrupts the gut microbiome, with the consequent intestinal inflammation and loss of barrier integrity driving chronic systemic inflammation that appears to dysregulate immunometabolic pathways, accelerating the ageing process and reducing lifespan 1,3-7 . Interestingly, epidemiological data suggest that Western diet-associated diseases are rising fastest in in the developing world 2,8 , regions where parasitic worms (helminths) and other infectious agents are being eradicated 9 . Helminths promote their survival by releasing excretory-secretory (ES) products that, by dampening inflammation and promoting tissue repair, act to prevent worm expulsion but also limit host pathology 10 . Thus, the relatively rapid eradication of these parasites appears to have resulted in hyper-active host immune systems, characterised by chronic low-grade inflammation that may (further) contribute to development of obesity and associated metabolic syndrome co-morbidities, as well as allergic and autoimmune inflammatory disorders, in developing and urbanised countries 10 . Whilst this has questioned the wisdom of current mass parasite eradication programs, it has emphasised the potential of utilising worm infections or ES to treat a wide range of noncommunicable diseases that are characterised by chronic inflammation [11][12][13] . Indeed, we have shown that a single, defined ES protein, ES-62, can suppress pathology in mouse models of allergic and autoimmune inflammatory diseases 9,10,14-16 . ES-62 achieves this by virtue of immunomodulatory phosphorylcholine groups attached...