Snell Terry W, Johnston Rachel K
School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
School of Biology, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
Exp Gerontol. 2014 Sep;57:47-56. doi: 10.1016/j.exger.2014.05.005. Epub 2014 May 14.
Diet has profound effects on animal longevity and manipulation of nutrient sensing pathways is one of the primary interventions capable of lifespan extension. This often is done through caloric restriction (CR) and a variety of CR mimics have been identified that produce life extending effects without adhering to the rigorous CR dietary regimen. Glycerol is a dietary supplement capable mimicking CR by shifting metabolism away from glycolysis and towards oxidative phosphorylation. Glycerol supplementation has a number of beneficial effects, including lifespan extension, improved stress resistance, and enhanced locomotory and mitochondria activity in older age classes. Using rotifers as a model, we show that supplements of 150-300mM glycerol produced 40-50% extension of mean lifespan. This effect was produced by raising glycerol concentration only three times higher than its baseline concentration in rotifer tissues. Glycerol supplementation decreased rotifer reliance on glycolysis and reduced the pro-aging effects of glucose. Glycerol also acted as a chemical chaperone, mitigating damage by protein aggregation. Glycerol treatment improved rotifer swimming performance in older age classes and maintained more mitochondrial activity. Glycerol treatment provided increased resistance to starvation, heat, oxidation, and osmotic stress, but not UV stress. When glycerol was co-administered with the hexokinase inhibitor 2-deoxyglucose, the lifespan extending effect of glycerol was enhanced. Co-administration of glycerol with inhibitors like 2-deoxyglucose can lower their efficacious doses, thereby reducing their toxic side effects.
饮食对动物寿命有着深远影响，而调节营养感知途径是能够延长寿命的主要干预措施之一。这通常通过热量限制（CR）来实现，并且已经鉴定出多种CR模拟物，它们无需严格遵循CR饮食方案就能产生延长寿命的效果。甘油是一种膳食补充剂，能够通过将代谢从糖酵解转向氧化磷酸化来模拟CR。补充甘油有许多有益效果，包括延长寿命、提高抗应激能力以及增强老年群体的运动和线粒体活性。以轮虫为模型，我们发现补充150 - 300mM甘油可使平均寿命延长40 - 50%。这种效果是通过将甘油浓度提高到仅比轮虫组织中的基线浓度高三倍而产生的。补充甘油降低了轮虫对糖酵解的依赖，并减少了葡萄糖的促衰老作用。甘油还作为一种化学伴侣，减轻蛋白质聚集造成的损伤。甘油处理改善了老年轮虫的游泳性能，并维持了更多的线粒体活性。甘油处理提高了对饥饿、热、氧化和渗透应激的抵抗力，但对紫外线应激没有作用。当甘油与己糖激酶抑制剂2 - 脱氧葡萄糖共同给药时，甘油的寿命延长效果增强。甘油与2 - 脱氧葡萄糖等抑制剂共同给药可以降低它们的有效剂量，从而减少它们的毒副作用。
