DNA damage has been hypothesized to be a driving force of the aging process. At the same time, there exists multiple compounds that can extend lifespan in model organisms, such as yeast, worms, flies, and mice. One possible mechanism of action for these compounds is a protective effect against DNA damage. We investigated whether five of these lifespan-extending compounds, dinitrophenol, metformin, rapamycin, resveratrol, and spermidine, could protect nuclear DNA in the yeast Saccharomyces cerevisiae at the same doses under which they confer lifespan extension. We found that rapamycin and spermidine were able to decrease the spontaneous mutation rate at the CAN1 locus, whereas dinitrophenol, metformin, and resveratrol were able to protect yeast against CAN1 mutations induced by ethyl methanesulfonate (EMS). We also tested whether these compounds could enhance survival against EMS, ultraviolet (UV) light, or hydrogen peroxide (H₂O₂) insult. All five compounds conferred a protective effect against EMS, while metformin and spermidine protected yeast against UV light. Somewhat surprisingly, none of the compounds were able to afford a significant protection against H₂O₂, with spermidine dramatically sensitizing cells. We also examined the ability of these compounds to increase lifespan when growth-arrested by hydroxyurea; only spermidine was found to have a positive effect. Overall, our results suggest that lifespan-extending compounds may act in part by protecting nuclear DNA.

DNA损伤被认为是衰老过程的驱动力。同时，存在多种可以延长模型生物寿命的化合物，例如酵母，蠕虫，果蝇和小鼠。这些化合物的一种可能的作用机理是对DNA损伤的保护作用。我们调查了这些延长寿命的化合物中的五个，二硝基苯酚，二甲双胍，雷帕霉素，白藜芦醇和亚精胺，是否可以相同的剂量保护啤酒酵母中的核DNA，从而延长了寿命。我们发现雷帕霉素和亚精胺能够降低CAN1基因座的自发突变率，而二硝基苯酚，二甲双胍和白藜芦醇能够保护酵母免受CAN1的侵害。甲磺酸乙酯（EMS）诱导的突变。我们还测试了这些化合物是否可以提高抵抗EMS，紫外线（UV）或过氧化氢（H ₂ O ₂）侵害的存活率。这五种化合物均具有针对EMS的保护作用，而二甲双胍和亚精胺可保护酵母免受紫外线侵害。出乎意料的是，没有一种化合物能够通过亚精胺使细胞显着敏化而对H ₂ O ₂提供明显的保护。当羟基脲阻止生长时，我们还研究了这些化合物增加寿命的能力。仅发现亚精胺具有积极作用。总体而言，我们的结果表明，延长寿命的化合物可能部分通过保护核DNA发挥作用。