Biology Letters ( IF 2.8 ) Pub Date : 2021-06-09 , DOI: 10.1098/rsbl.2020.0916 Jessica Dysarz 1 , Georg Fuellen 2 , Steffen Möller 2 , Walter Luyten 3 , Christian Schmitz-Linneweber 1 , Nadine Saul 1
Recently, nine Caenorhabditis elegans genes, grouped into two pathways/clusters, were found to be implicated in healthspan in C. elegans and their homologues in humans, based on literature curation, WormBase data mining and bioinformatics analyses. Here, we further validated these genes experimentally in C. elegans. We downregulated the nine genes via RNA interference (RNAi), and their effects on physical function (locomotion in a swim assay) and on physiological function (survival after heat stress) were analysed in aged nematodes. Swim performance was negatively affected by the downregulation of acox-1.1, pept-1, pak-2, gsk-3 and C25G6.3 in worms with advanced age (twelfth day of adulthood) and heat stress resistance was decreased by RNAi targeting of acox-1.1, daf-22, cat-4, pig-1, pak-2, gsk-3 and C25G6.3 in moderately (seventh day of adulthood) or advanced aged nematodes. Only one gene, sad-1, could not be linked to a health-related function in C. elegans with the bioassays we selected. Thus, most of the healthspan genes could be re-confirmed by health measurements in old worms.
中文翻译:
与秀丽隐杆线虫和人类健康有关的基因调节老年秀丽隐杆线虫的抗应激能力和身体能力
最近,根据文献整理、WormBase 数据挖掘和生物信息学分析,发现 9 个秀丽隐杆线虫基因(分为两个途径/簇)与秀丽隐杆线虫及其人类同源物的健康寿命有关。在这里,我们进一步在秀丽隐杆线虫中通过实验验证了这些基因。我们通过 RNA 干扰 (RNAi) 下调了这 9 个基因,并在老年线虫中分析了它们对身体功能(游泳试验中的运动)和生理功能(热应激后的生存)的影响。高龄(成年第十二天)线虫中acox-1.1 、 pept-1 、 pak-2 、 gsk-3和C25G6.3的下调对游泳表现产生负面影响,并且针对acox的 RNAi 降低了热应激抵抗力-1.1 、 daf-22 、 cat-4 、 pig-1 、 pak-2 、 gsk-3和C25G6.3中度(成年第七天)或晚期线虫。通过我们选择的生物测定,只有一个基因( sad-1 )无法与秀丽隐杆线虫中的健康相关功能联系起来。因此,大多数健康跨度基因可以通过老蠕虫的健康测量来重新确认。