Pandey Renu, Sharma Meenakshi, Saluja Daman
Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi -07, India.
Aging (Albany NY). 2018 Dec 12;10(12):3910-3937. doi: 10.18632/aging.101682.
Aging/senescence includes not just decline in lifespan but also etiologies of age associated morbidities which are inadequately understood. Extensive research has been undertaken to delineate the pathways and generate mutants with extended lifespan. However, little is known about the health status of these long lived mutants in the background of important genetic perturbations. is one of the leading model organisms to study aging. Deletion of SIN-3, a transcription coregulator in has been shown to reduce the lifespan of the mutant worms by half as compared to the wild-type and isogenic controls. The current study focuses on the effect of SIN-3 deletion on the healthspan of the worms. We find that not only are mutants more susceptible to stress, but the overall stress intolerance and physiological decline is sex dependent. The severity of the phenotype is more pronounced in hermaphrodites as compared to the males carrying the same mutation with respect to the controls. The results further suggest that genetic perturbation along with the gender play an important role in determining the lifespan, healthspan and overall fitness of an organism.
衰老/老化不仅包括寿命的缩短,还包括与年龄相关的发病率的病因,而这些病因目前还没有得到充分的了解。人们已经进行了广泛的研究来描绘相关途径并培育出寿命延长的突变体。然而,对于这些长寿突变体在重要基因扰动背景下的健康状况却知之甚少。秀丽隐杆线虫是研究衰老的主要模式生物之一。已证明,秀丽隐杆线虫中的转录共调节因子SIN-3缺失后,与野生型和同基因对照相比,突变蠕虫的寿命缩短了一半。当前的研究聚焦于SIN-3缺失对蠕虫健康期的影响。我们发现,SIN-3突变体不仅更容易受到压力影响,而且整体的压力不耐受和生理衰退还取决于性别。与携带相同突变的雄性相比,该表型在雌雄同体中的严重程度相对于对照更为明显。结果进一步表明,基因扰动和性别在决定生物体的寿命、健康期和整体适应性方面起着重要作用。