| Added by | Patrick.Jouandin |
|---|---|
| Group name | EquipePJ |
| Item Type | Journal Article |
| Title | A genetic model of methionine restriction extends Drosophila health- and lifespan |
| Creator | Parkhitko et al. |
| Author | Andrey A. Parkhitko |
| Author | Lin Wang |
| Author | Elizabeth Filine |
| Author | Patrick Jouandin |
| Author | Dmitry Leshchiner |
| Author | Richard Binari |
| Author | John M. Asara |
| Author | Joshua D. Rabinowitz |
| Author | Norbert Perrimon |
| Abstract | Loss of metabolic homeostasis is a hallmark of aging and is characterized by dramatic metabolic reprogramming. To analyze how the fate of labeled methionine is altered during aging, we applied 13C5-Methionine labeling to Drosophila and demonstrated significant changes in the activity of different branches of the methionine metabolism as flies age. We further tested whether targeted degradation of methionine metabolism components would "reset" methionine metabolism flux and extend the fly lifespan. Specifically, we created transgenic flies with inducible expression of Methioninase, a bacterial enzyme capable of degrading methionine and revealed methionine requirements for normal maintenance of lifespan. We also demonstrated that microbiota-derived methionine is an alternative and important source in addition to food-derived methionine. In this genetic model of methionine restriction (MetR), we also demonstrate that either whole-body or tissue-specific Methioninase expression can dramatically extend Drosophila health- and lifespan and exerts physiological effects associated with MetR. Interestingly, while previous dietary MetR extended lifespan in flies only in low amino acid conditions, MetR from Methioninase expression extends lifespan independently of amino acid levels in the food. Finally, because impairment of the methionine metabolism has been previously associated with the development of Alzheimer's disease, we compared methionine metabolism reprogramming between aging flies and a Drosophila model relevant to Alzheimer's disease, and found that overexpression of human Tau caused methionine metabolism flux reprogramming similar to the changes found in aged flies. Altogether, our study highlights Methioninase as a potential agent for health- and lifespan extension. |
| Publication | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 118 |
| Issue | 40 |
| Pages | e2110387118 |
| Date | 2021-10-05 |
| Journal Abbr | Proc Natl Acad Sci U S A |
| Language | eng |
| DOI | 10.1073/pnas.2110387118 |
| ISSN | 1091-6490 |
| Library Catalog | PubMed |
| Extra | PMID: 34588310 PMCID: PMC8501845 |
| Tags | 13C-Methionine labeling, Aging, Alzheimer Disease, Alzheimer's disease, Amino Acids, Animals, Animals, Genetically Modified, Carbon-Sulfur Lyases, Drosophila, Food, Humans, Longevity, Methioninase, Methionine, methionine restriction, Models, Genetic, original |
| Date Added | 2023/02/17 - 16:44:31 |
| Date Modified | 2023/02/17 - 16:44:31 |
| Notes and Attachments | Full Text (Attachment) PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
