Aufgrund von Vorbereitungen auf eine neue Version von KOPS, können kommenden Montag und Dienstag keine Publikationen eingereicht werden. (Due to preparations for a new version of KOPS, no publications can be submitted next Monday and Tuesday.)
Type of Publication: | Journal article |
Publication status: | Published |
URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-2-112i8hdxrqulm8 |
Author: | Parkhitko, Andrey A.; Ramesh, Divya; Wang, Lin; Leshchiner, Dmitry; Filine, Elizabeth; Binari, Richard; Olsen, Abby L.; Asara, John M.; Cracan, Valentin; Perrimon, Norbert et al. |
Year of publication: | 2020 |
Published in: | eLife ; 9 (2020). - e58053. - eLife Sciences Publications. - eISSN 2050-084X |
Pubmed ID: | 33319750 |
DOI (citable link): | https://dx.doi.org/10.7554/eLife.58053 |
Summary: |
Aging is characterized by extensive metabolic reprogramming. To identify metabolic pathways associated with aging, we analyzed age-dependent changes in the metabolomes of long-lived Drosophila melanogaster. Among the metabolites that changed, levels of tyrosine were increased with age in long-lived flies. We demonstrate that the levels of enzymes in the tyrosine degradation pathway increase with age in wild-type flies. Whole-body and neuronal-specific downregulation of enzymes in the tyrosine degradation pathway significantly extends Drosophila lifespan, causes alterations of metabolites associated with increased lifespan, and upregulates the levels of tyrosine-derived neuromediators. Moreover, feeding wild-type flies with tyrosine increased their lifespan. Mechanistically, we show that suppression of ETC complex I drives the upregulation of enzymes in the tyrosine degradation pathway, an effect that can be rescued by tigecycline, an FDA-approved drug that specifically suppresses mitochondrial translation. In addition, tyrosine supplementation partially rescued lifespan of flies with ETC complex I suppression. Altogether, our study highlights the tyrosine degradation pathway as a regulator of longevity.
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Subject (DDC): | 570 Biosciences, Biology |
Link to License: | Attribution 4.0 International |
Bibliography of Konstanz: | Yes |
Refereed: | Yes |
PARKHITKO, Andrey A., Divya RAMESH, Lin WANG, Dmitry LESHCHINER, Elizabeth FILINE, Richard BINARI, Abby L. OLSEN, John M. ASARA, Valentin CRACAN, Norbert PERRIMON, 2020. Downregulation of the tyrosine degradation pathway extends Drosophila lifespan. In: eLife. eLife Sciences Publications. 9, e58053. eISSN 2050-084X. Available under: doi: 10.7554/eLife.58053
@article{Parkhitko2020Downr-52405, title={Downregulation of the tyrosine degradation pathway extends Drosophila lifespan}, year={2020}, doi={10.7554/eLife.58053}, volume={9}, journal={eLife}, author={Parkhitko, Andrey A. and Ramesh, Divya and Wang, Lin and Leshchiner, Dmitry and Filine, Elizabeth and Binari, Richard and Olsen, Abby L. and Asara, John M. and Cracan, Valentin and Perrimon, Norbert}, note={Article Number: e58053} }
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