The molecular mechanisms underlying the longevity and health promoting effects of the triterpenoid ursolic acid in Drosophila melanogaster
Final Report Abstract
In the present project, the goal was to investigate the molecular mechanisms underlying the longevity and health promoting effects of the triterpenoid ursolic acid (UA) in the model organism D. melanogaster. To this end, we followed three approaches. First, we examined, whether UA affects body composition and energy expenditure of flies. Thereby we could show, that UA increases food intake and modulates energy metabolism in male flies while total body weight remains largely unchanged. Secondly, we explored whether UA promotes longevity and healthy ageing under different dietary regimens and treatments. Moreover, by using functional senescence analyses we examined, whether supplementation of UA was able to improve parameters that undergo a gradual age-dependent decline such as locomotor activity, immune status, gut integrity, stress resistance and male fecundity. Our data indicate, that UA ingestion increases the life span and climbing activity, induces the expression of Spargel (srl, PGC1αorthologue), partly improves immune function but does not improve oxidative stress resistance and gut health. Furthermore, male fecundity was not affected by UA, irrespective of the upregulation of usp expression level. Thirdly and importantly, we tested the impact of UA in D. melanogaster mutants with different lifespan-associated genetic backgrounds. We could show by using srl mutants and the application of antibiotics, that the enhancing effect of UA on both life span and climbing activity depends on induction of srl expression and the presence of a normal gut microbiota. Thus, with our findings we provide mechanistic insights by which UA may improve health span and survival in D. melanogaster. Moreover, we examined a structure derivate of UA – lithocholic acid (LCA) – in terms of survival and affected pathways. Similarly, to UA LCA significantly induces the mean, the median, and the maximum survival in male D. melanogaster. Our data suggest that besides an upregulation of srl, unidentified alterations in the structure or metabolism of the gut microbiota contribute to the longevity effect mediated by LCA. Overall, our findings contribute to a better understanding of the ageing process in general and to the life prolonging properties of UA and LCA in the model organism Drosophila melanogaster.
Publications
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(2018) Lithocholic Acid Improves the Survival of Drosophila melanogaster Mol Nutr Food Res. 62(20): e1800424
Staats S, Rimbach G, Kuenstner A, Graspeuntner S, Rupp J, Busch H, Sina C, Ipharraguerre IR, Wagner AE
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(2019) Dietary ursolic acid improves health span and life span in male Drosophila melanogaster. Biofactors, 45(2): 169-186
Staats S, Wagner AE, Lüersen K, Künstner A, Meyer T, Kahns AK, Derer S, Graspeuntner S, Rupp J, Busch H, Sina C, Ipharraguerre IR, Rimbach G
