Dietary ursolic acid improves health span and life span in male Drosophila melanogaster

Abstract

The health and life span of Drosophila melanogaster are partly determined by intestinal barrier integrity, metabolic rate as well as stress response and the expression of longevity‐associated genes, depending on genetic and dietary factors. Ursolic acid (UA) is a naturally occurring triterpenoid exhibiting potential antimicrobial, anti‐inflammatory, and antiobesity activity and counteracting age‐related deficits in muscle strength. In this study, UA was dietarily administered to w1118 D. melanogaster which significantly elongated the health and life span of males. Spargel (srl) is the Drosophila orthologue of mammalian peroxisome proliferator‐activated receptor‐gamma coactivator 1 α(PGC1α), an important regulator of energy homeostasis and mitochondrial function. Our results indicate that the health‐promoting effect of UA, demonstrated by a significant increase in climbing activity, occurs via an upregulation of srl expression leading to a metabolic shift in the fly without reducing fecundity or gut integrity. Moreover, UA affected the flies' microbiota in a manner that contributed to life span extension. Srl expression and microbiota both seem to be affected by UA, as we determined by using srl‐mutant and axenic flies. © 2018 BioFactors, 45(2):169–186, 2019

Minimal effects ofspargel(PGC-1) overexpression in aDrosophilamitochondrial disease model

“…Although mitochondrial biogenesis is reciprocally affected by PGC-1α knockout (Lin et al, 2004; Leone et al, 2005) and overexpression (Lehman et al, 2000; Lin et al, 2002), the PGC-1 family also impacts thermogenesis in brown fat (Uldry et al, 2006), neuromuscular differentiation (Lin et al, 2002; Handschin et al, 2007), hepatic gluconeogenesis (Yoon et al, 2001) and oxygen radical detoxification (St-Pierre et al, 2006). As a coactivator, PGC-1 interacts with sequence-specific transcription factors which specify the genes to be regulated, but the known transcriptional targets of srl are not limited to those involved in mitochondrial biogenesis (Tiefenböck et al, 2010), and it has elsewhere been implicated in various cell differentiation and cell survival programs, or in functional maintenance during aging (Tinkerhess et al, 2012;Wagner et al, 2015; Merzetti and Staveley, 2015; Diop et al, 2015; Ng et al, 2017; Staats et al, 2018). Rera et al (2011) reported an increase in mitochondrial markers in flies globally overexpressing srl .…”

Terpenoids as Potential Geroprotectors

“…In Drosophila , ursolic acid increases in climbing activity. Furthermore, this triterpenoid led to flies’ microbiota changes that contribute to life- and healthspan extension [ 281 ]. Maslinic acid sufficiently improved mobility in the elderly.…”

“…Triterpenoids and triterpenoid-containing extracts stimulate expression and enhance enzymatic activity of pro-longevity proteins SIRT1, SIRT6, PGC-1α, and JNK [ 251 , 265 , 275 , 281 , 296 , 297 , 298 ]. Furthermore, in silico, in vitro, and in vivo experiments demonstrated that ursolic acid directly binds to the outer surface of mammalian SIRT1 [ 297 ], as well as links with nematode JNK-1 ATP-binding site [ 250 ].…”

Drosophila melanogaster as an alternative model organism in nutrigenomics

“…The authors observed a 100-fold induction in the total abundance of bacterial members of the Drosophila microbiota by increasing dietary yeast from 4 to 27% in the fly food [84]. In another study, the bioactive compound ursolic acid has been added to the fruit fly diet, which resulted in a shift of the gut microbial composition mainly affecting Lactobacillus, Acetobacter, and Actinobacteria, potentially related to an increased life span and climbing activity, as well as an overexpression of the Spargel gene (PPARγ-coactivator 1 α (PGC-1α) homolog) in the male fruit fly [85].…”

“…Although this method does not deliver direct phylogenetic information, it provides information about relative subcommunity abundance and absolute cell numbers at-line through distinct light scatter and fluorescence properties [88]. Staats and colleagues have already used a flow cytometry-based analysis together with the sequencing of the V1-V2 regions of the 16S rRNA to detect changes in the microbiome of Drosophila melanogaster following the intake of the plant bioactive ursolic acid [85].…”