PreprintArticleVersion 1This version is not peer-reviewed
Longevity Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements in y w Male Drosophila melanogaster
Version 1
: Received: 24 August 2024 / Approved: 26 August 2024 / Online: 26 August 2024 (17:13:59 CEST)
How to cite:
Bearden, A. A.; Stewart, E. M.; Casher, C. C.; Shaddix, M. A.; Nobles, A. C.; Mockett, R. J. Longevity Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements in y w Male Drosophila melanogaster. Preprints2024, 2024081876. https://doi.org/10.20944/preprints202408.1876.v1
Bearden, A. A.; Stewart, E. M.; Casher, C. C.; Shaddix, M. A.; Nobles, A. C.; Mockett, R. J. Longevity Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements in y w Male Drosophila melanogaster. Preprints 2024, 2024081876. https://doi.org/10.20944/preprints202408.1876.v1
Bearden, A. A.; Stewart, E. M.; Casher, C. C.; Shaddix, M. A.; Nobles, A. C.; Mockett, R. J. Longevity Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements in y w Male Drosophila melanogaster. Preprints2024, 2024081876. https://doi.org/10.20944/preprints202408.1876.v1
APA Style
Bearden, A. A., Stewart, E. M., Casher, C. C., Shaddix, M. A., Nobles, A. C., & Mockett, R. J. (2024). Longevity Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements in y w Male Drosophila melanogaster. Preprints. https://doi.org/10.20944/preprints202408.1876.v1
Chicago/Turabian Style
Bearden, A. A., Amber C. Nobles and Robin J. Mockett. 2024 "Longevity Effects of Target of Rapamycin and Phosphatidylinositol 3-Kinase Inhibitors and Other Autophagy-Related Supplements in y w Male Drosophila melanogaster" Preprints. https://doi.org/10.20944/preprints202408.1876.v1
Abstract
Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived y w test strain, screening was performed in male flies supplemented either throughout adulthood or in a few cases beginning in middle or late adult life, with concentrations spanning 4-6 orders of magnitude in most cases. Supplementation with PP242 and deferiprone, an iron chelator, beginning in late adult life had no positive effect on life span. Lifelong supplementation with Ku-0063794, LY294002, PX-866-17OH, Torin2 and WYE-28 had no effect at any dose. Rapamycin, spermidine and wortmannin all had significant life-shortening effects at the highest doses tested. AZD8055, PI-103 hydrochloride and WYE-132 yielded slight beneficial effects at 1-2 doses, but only 100 nM AZD8055 was confirmed to have a minor (1.3%) effect in a replicate experiment, which was encompassed by other control groups within the same study. These compounds had no effect on fly fecundity (egg-laying) or fertility (development of progeny to adulthood), but equivalent doses of rapamycin abolished fertility. The solvent DMSO had no significant effect on life span at the concentrations used to solubilize most compounds in the fly medium, but it drastically curtailed both survival and fertility at higher concentrations. 2-hydroxypropyl-β-cyclodextrin also failed to extend the life span when provided throughout adulthood or beginning in mid-adult life. Collectively, the results suggest that inhibition of the TOR/PI3K pathway and autophagy through dietary intervention is not a straightforward anti-aging strategy in Drosophila, and that further extension of life is difficult in comparatively long-lived flies.
Keywords
life span; aging; Drosophila; rapamycin; TOR inhibition
Subject
Biology and Life Sciences, Aging
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
