Caloric restriction (CR) is one of the most effective interventions to prolong lifespan and promote health. Recently, it has been suggested that hydrogen sulfide (H₂S) may play a pivotal role in mediating some of these CR-associated benefits. While toxic at high concentrations, H₂S at lower concentrations can be biologically advantageous. H₂S levels can be artificially elevated via H₂S-releasing donor drugs. In this study, we explored the function of a novel, slow-releasing H₂S donor drug (FW1256) and used it as a tool to investigate H₂S in the context of CR and as a potential CR mimetic. We show that exposure to FW1256 extends lifespan and promotes health in Caenorhabditis elegans (C. elegans) more robustly than some previous H₂S-releasing compounds, including GYY4137. We looked at the extent to which FW1256 reproduces CR-associated physiological effects in normal-feeding C. elegans. We found that FW1256 promoted healthy longevity to a similar degree as CR but with fewer fitness costs. In contrast to CR, FW1256 actually enhanced overall reproductive capacity and did not reduce adult body length. FW1256 further extended the lifespan of already long-lived eat-2 mutants without further detriments in developmental timing or fertility, but these lifespan and healthspan benefits required H₂S exposure to begin early in development. Taken together, these observations suggest that FW1256 delivers exogenous H₂S efficiently and supports a role for H₂S in mediating longevity benefits of CR. Delivery of H₂S via FW1256, however, does not mimic CR perfectly, suggesting that the role of H₂S in CR-associated longevity is likely more complex than previously described.

热量限制（CR）是延长寿命和促进健康的最有效干预措施之一。最近，有人提出，硫化氢（H ₂ S）在介导这些CR相关的益处中可能起关键作用。虽然在高浓度下有毒，但较低浓度的H ₂ S在生物学上可能是有利的。可以通过释放H ₂ S的供体药物人为地提高H ₂ S的水平。在这项研究中，我们探索了一种新型的缓释H ₂ S供体药物（FW1256）的功能，并将其用作研究H ₂的工具。S在CR的上下文中并作为潜在的CR模拟。我们显示暴露于FW1256可以延长秀丽隐杆线虫（C. elegans）的寿命，并比某些以前的H ₂ S释放化合物（包括GYY4137 ）更健康。我们研究了FW1256在正常喂养的秀丽隐杆线虫中繁殖CR相关生理效应的程度。我们发现FW1256可以将健康长寿提高到与CR相似的程度，但健身成本却更低。与CR相比，FW1256实际上增强了整体生殖能力，并且没有减少成人的体长。FW1256进一步延长了已经寿命很长的eat-2的寿命没有发育时间或生育，但这些寿命和长期保健福利的进一步利弊突变体需要■ ₂风险敞口，以在开发早期开始。综上所述，这些观察结果表明FW1256有效地传递外源H ₂ S并支持H ₂ S在介导CR的长寿益处方面的作用。但是，通过FW1256输送H ₂ S不能完美地模拟CR，这表明H ₂ S在与CR相关的寿命中的作用可能比以前描述的更为复杂。