Data from: Hormesis results in trade-offs with immunity

Many have argued that we may be able to extend life and improve human health through hormesis, the beneficial effects of low-level toxins and other stressors. But, studies of hormesis in model systems have not yet established whether stress-induced benefits are cost free, artifacts of inbreeding, or come with deleterious side effects. Here, we provide evidence that hormesis results in trade-offs with immunity. We find that a single topical dose of dead spores of the entomopathogenic fungus, Metarhizium robertsii, increases the longevity of the fruit fly, Drosophila melanogaster, without significant decreases in fecundity. We find that hormetic benefits of pathogen challenge are greater in lines that lack key components of antifungal immunity (Dif and Turandot M). And, in outbred fly lines, we find that topical pathogen challenge enhances both survival and fecundity, but reduces ability to fight off live infections. The results provide evidence that hormesis is manifested by stress-induced trade-offs with immunity, not cost-free benefits or artifacts of inbreeding. Our findings illuminate mechanisms underlying pathogen-induced life-history trade-offs, and indicate that reduced immune function may be an ironic side effect of the “elixirs of life.”

诸多学者提出，可通过毒物兴奋效应（hormesis）延长人类寿命、改善健康状况，该效应指低剂量毒素与其他应激原所诱导的有益作用。然而，当前基于模式生物系统的毒物兴奋效应研究尚未明确：应激诱导的益处究竟是无成本收益、近交产生的人为假象，还是伴随有害副作用的效应。本研究提供证据表明，毒物兴奋效应会引发免疫功能相关的生存权衡。我们发现，单次局部施用昆虫病原真菌（entomopathogenic fungus）罗伯茨绿僵菌（Metarhizium robertsii）的死孢子，可延长黑腹果蝇（Drosophila melanogaster）的寿命，且不会显著降低其繁殖力。进一步研究显示，在缺乏抗真菌免疫关键组分Dif与Turandot M的果蝇品系中，病原体激发所带来的毒物兴奋效应益处更为显著。此外，在远交系果蝇中，局部病原体激发可同时提升果蝇的存活率与繁殖力，但会降低其抵御活病原体感染的能力。本研究结果证实，毒物兴奋效应的本质为应激诱导的免疫权衡，而非无成本收益或近交产生的人为假象。我们的研究阐明了病原体诱导的生活史权衡背后的机制，并揭示免疫功能受损或许是这类"长生不老灵药"颇具讽刺意味的副作用。