
@article {86474,
	title = {Downregulation of the tyrosine degradation pathway extends  lifespan.},
	journal = {Elife},
	volume = {9},
	year = {2020},
	month = {2020 Dec 15},
	abstract = {<p>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 . 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 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.</p>
},
	issn = {2050-084X},
	doi = {10.7554/eLife.58053},
	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 Rabinowitz, Joshua D and Brockmann, Axel and Perrimon, Norbert}
}
