RESUMEN
The transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the main downstream effectors of the evolutionarily conserved Hippo signaling pathway. YAP/TAZ are implicated in the transcriptional regulation of target genes that are involved in a wide range of key biological processes affecting tissue homeostasis and play dual roles in the aging process, depending on the cellular and tissue context. The aim of the present study was to investigate whether pharmacological inhibitors of Yap/Taz increase the lifespan of Drosophila melanogaster. Real-time qRT-PCR was performed to measure the changes in the expression of Yki (Yorkie, the Drosophila homolog of YAP/TAZ) target genes. We have revealed a lifespan-increasing effect of YAP/TAZ inhibitors that was mostly associated with decreased expression levels of the wg and E2f1 genes. However, further analysis is required to understand the link between the YAP/TAZ pathway and aging.
Asunto(s)
Antineoplásicos , Drosophila melanogaster , Animales , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Transactivadores/genética , Transactivadores/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Proteínas Señalizadoras YAP , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Drosophila/metabolismoRESUMEN
Honeysuckle Lonicera pallasii (Lonicera caerulea L.) is an excellent source of anthocyanins which have a number of health-promoting properties mainly associated with antioxidant and anti-inflammatory activities. Cyanidin-3-O-glucoside (C3G) is one of the most common anthocyanins naturally found in honeysuckle. The goal of the present study was to investigate antioxidant and anti-aging properties of Lonicera pallasii (Lonicera caerulea L.) extract (LE) and C3G using red blood cells (RBC) and Drosophila melanogaster models. LE and C3G treatment at a concentration of 100 µM induced enhancement of median and maximum lifespan up to 8%. LE and C3G supplementation at a concentration of 100 µM increased stress resistance up to 10%. The locomotor activity decreased during LE and C3G treatment in 4 and 6 weeks up to 52% in females. The integrity of the intestinal barrier was increased by 4% after LE treatment. These effects were accompanied by increased expression of Hif1 (pro-longevity gene) in response to C3G treatment and decreased expression of Keap1 (anti-longevity gene) after C3G and LE supplementation. RNA interference-mediated knockdown of Sirt6 completely abolished the positive effect obtained of LE and C3G supplementation in males which indicates that lifespan-extending effect is associated with Sirt6 activation. The experiments on the various in-vitro models (including radical scavenging activity and oxidative hemolysis of RBC demonstrated antioxidant and membrane-protective activities of LE and C3G. The present study indicates that Lonicera extract can prolong the lifespan and improve the healthspan of Drosophila model through biological and antioxidant activities.