Increased availability of cannabis and cannabinoid-containing products necessitates the need for an understanding of how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to different concentrations of THC (0.08, 0.4, 2 μM) during embryonic-larval development and the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation). Exposure to 0.08 μM THC resulted in increased male survival at 30 months of age. As the concentration of THC increased, this protective effect was lost. Treatment with the lowest concentration of THC also significantly increased egg production, while higher concentrations resulted in impaired fecundity. Treatment with the lowest dose of THC significantly reduced wet weight, the incidence of kyphosis, and the expression of several senescence and inflammatory markers (p16^ink4ab, tnfα, il-1β, il-6, pparα and pparγ) in the liver, but not at higher doses indicating a biphasic or hormetic effect. Exposure to THC did not affect the age-related reductions in locomotor behavior. Within the F1 generation, many of these changes were not observed. However, the reduction in fecundity due to THC exposure was worse in the F1 generation because offspring whose parents received high dose of THC were completely unable to reproduce. Together, our results demonstrate that a developmental exposure to THC can cause significant effects on longevity and healthspan of zebrafish in a biphasic manner.

中文翻译：

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发育过程中接触 Δ9-四氢大麻酚 (THC) 会对老年斑马鱼 (Danio rerio) 的寿命、炎症和繁殖产生双相影响。


大麻和含大麻素产品的供应量增加使得有必要了解这些物质如何影响衰老。在这项研究中，斑马鱼（ Danio rerio ）在胚胎幼虫发育过程中暴露于不同浓度的 THC（0.08、0.4、2 μM），并在 30 个月后测量了对衰老的影响以及暴露鱼的后代（F1 代） ）。暴露于 0.08 μM THC 会导致雄性 30 月龄时的存活率增加。随着 THC 浓度的增加，这种保护作用就会消失。用最低浓度的四氢大麻酚处理也显着增加了产蛋量，而较高浓度的四氢大麻酚则导致繁殖力受损。使用最低剂量的 THC 治疗可显着降低湿重、脊柱后凸的发生率以及肝脏中几种衰老和炎症标志物（ p16 ^ink4ab 、 tnfα 、 il-1β 、 il-6 、 pparα和pparγ ）的表达，但没有效果较高剂量表明存在双相或兴奋效应。接触 THC 不会影响与年龄相关的运动行为减少。在 F1 代中，许多这些变化都没有被观察到。然而，F1 代由于 THC 暴露导致的繁殖力下降更为严重，因为父母接受高剂量 THC 的后代完全无法繁殖。总之，我们的结果表明，发育过程中接触 THC 可以以双相方式对斑马鱼的寿命和健康产生重大影响。