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 w 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.
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