抗衰老药物对线虫生存曲线影响的荟萃分析

随着世界人口老龄化步伐的加快,衰老机制及抗衰老药物的研究日益成为生物医学领域的热点前沿之一.国内外已有大量研究报道抗衰老药物能够延长多种模式生物包括线虫、果蝇、小鼠、大鼠及灵长类等的寿命,然而,这些药物延缓衰老方式的差异仍缺乏系统研究.因此,本研究以衰老研究的热点模式生物线虫为对象,搜集1990年以来国内外刊物上正式发表的有关抗衰老药物寿命试验的研究文献及其涉及的生存曲线,利用荟萃分析比较了不同抗衰老药物与生存曲线变化类型间的关系,并结合药物的药理作用探讨其延寿机制.生存曲线特征聚类结果与药物生物学分类交叉分析结果表明,药理作用类型与增益类型具有很强相关性,提示这2种分类方法的结果是匹配的.抗氧化剂类药物和控制血糖类药物对生存曲线的改善总体增益虽然不是最高,但相对于正常组生存曲线其增益部分呈平移形,表明该类药物可以通过改善年龄结构对整个群体产生显著增益,且其衰老曲线的特征与自然衰老相似.抗癫痫药物及胃肠道菌群相关药物总体增益较大,其曲线增益形状呈梯形,提示该类药物(尤其是胃肠道菌群相关药物)尽管显著延长了少数个体的最大寿命,但是从整个群体来看,大多数个体寿命延长程度并不明显,受益的少数个体可能需要较长的外界资源支持方能保持较长时间的存活状态,这种模式既不大众化也不经济.综上所述,清除自由基和控制血糖类药物对健康老年有着更为积极合理的作用与效应.

Meta-analytic Insights into the Effects of Different Anti-aging Drugs on Survival Curves of Caenorhabditis elegans

Survival records of longevity experiments remain the most indispensable method in aging-related research in spite of the development of technology. A variety of interventions have been shown to extend the lifespan of C. elegans, including drugs, genetic controls, dietary restriction and so on. However, surprisingly there have been very few cross-study analyses to determine the pattern differences of these anti-aging strategies in survival curves. Here, we address this question by conducting a comprehensive and comparative meta-analysis on a wealth of published studies. Overall, the culture temperature plays a key role in the lifespan determination of normal C. elegans. We further analyse the variations in survival within drugs, and the cross-study results indicate that antioxidant and hypoglycemic agents show their advantages in improving the population though they only moderately increase overall lifespan. Drugs that improve gastrointestinal flora state extend maximum lifespan but many individual deaths occur in early time of the lifespan. Overall, antioxidant and hypoglycemic agents tend to be more reasonable and healthy in extending lifespan and anti-aging. Our work provides a new perspective and methodology to investigate lifespan- and aging-related diseases.