@article{4016,
  keywords = {Animals, Drosophila melanogaster, Aging, Longevity, Mitochondria, Tyrosine, Electron Transport Chain Complex Proteins, Tigecycline, Tyrosine Transaminase},
  author = {Andrey Parkhitko and Divya Ramesh and Lin Wang and Dmitry Leshchiner and Elizabeth Filine and Richard Binari and Abby Olsen and John Asara and Valentin Cracan and Joshua Rabinowitz and Axel Brockmann and Norbert Perrimon},
  title = {Downregulation of the tyrosine degradation pathway extends  lifespan.},
  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> },
  year = {2020},
  journal = {Elife},
  volume = {9},
  month = {2020 Dec 15},
  issn = {2050-084X},
  doi = {10.7554/eLife.58053},
  language = {eng},
}