IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44343-3.html
   My bibliography  Save this article

OXR1 maintains the retromer to delay brain aging under dietary restriction

Author

Listed:
  • Kenneth A. Wilson

    (Buck Institute for Research on Aging
    University of Southern California)

  • Sudipta Bar

    (Buck Institute for Research on Aging)

  • Eric B. Dammer

    (Emory University School of Medicine)

  • Enrique M. Carrera

    (Buck Institute for Research on Aging)

  • Brian A. Hodge

    (Buck Institute for Research on Aging)

  • Tyler A. U. Hilsabeck

    (Buck Institute for Research on Aging
    University of Southern California)

  • Joanna Bons

    (Buck Institute for Research on Aging)

  • George W. Brownridge

    (Buck Institute for Research on Aging)

  • Jennifer N. Beck

    (Buck Institute for Research on Aging)

  • Jacob Rose

    (Buck Institute for Research on Aging)

  • Melia Granath-Panelo

    (Buck Institute for Research on Aging)

  • Christopher S. Nelson

    (Buck Institute for Research on Aging)

  • Grace Qi

    (Buck Institute for Research on Aging)

  • Akos A. Gerencser

    (Buck Institute for Research on Aging)

  • Jianfeng Lan

    (Buck Institute for Research on Aging
    The Afilliated Hospital of Guilin Medican University)

  • Alexandra Afenjar

    (Groupe Hospitalier Universitaire
    Sorbonne Universités, Hôpital Trousseau)

  • Geetanjali Chawla

    (School of Natural Sciences, Shiv Nadar Institute of Eminence)

  • Rachel B. Brem

    (Buck Institute for Research on Aging
    University of Southern California
    University of California, Berkeley)

  • Philippe M. Campeau

    (Centre Hospitalier Universitaire Saint-Justine Research Center, CHU Sainte-Justine)

  • Hugo J. Bellen

    (Texas Children’s Hospital, Baylor College of Medicine)

  • Birgit Schilling

    (Buck Institute for Research on Aging)

  • Nicholas T. Seyfried

    (Emory University School of Medicine)

  • Lisa M. Ellerby

    (Buck Institute for Research on Aging
    University of Southern California)

  • Pankaj Kapahi

    (Buck Institute for Research on Aging
    University of Southern California)

Abstract

Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity.

Suggested Citation

  • Kenneth A. Wilson & Sudipta Bar & Eric B. Dammer & Enrique M. Carrera & Brian A. Hodge & Tyler A. U. Hilsabeck & Joanna Bons & George W. Brownridge & Jennifer N. Beck & Jacob Rose & Melia Granath-Pane, 2024. "OXR1 maintains the retromer to delay brain aging under dietary restriction," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44343-3
    DOI: 10.1038/s41467-023-44343-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44343-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44343-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alexander Lachmann & Denis Torre & Alexandra B. Keenan & Kathleen M. Jagodnik & Hoyjin J. Lee & Lily Wang & Moshe C. Silverstein & Avi Ma’ayan, 2018. "Massive mining of publicly available RNA-seq data from human and mouse," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    2. Joseph H.A. Vissers & Samuel A. Manning & Aishwarya Kulkarni & Kieran F. Harvey, 2016. "A Drosophila RNAi library modulates Hippo pathway-dependent tissue growth," Nature Communications, Nature, vol. 7(1), pages 1-6, April.
    3. Lawrence A. David & Corinne F. Maurice & Rachel N. Carmody & David B. Gootenberg & Julie E. Button & Benjamin E. Wolfe & Alisha V. Ling & A. Sloan Devlin & Yug Varma & Michael A. Fischbach & Sudha B. , 2014. "Diet rapidly and reproducibly alters the human gut microbiome," Nature, Nature, vol. 505(7484), pages 559-563, January.
    4. Nicolas Nègre & Christopher D. Brown & Lijia Ma & Christopher Aaron Bristow & Steven W. Miller & Ulrich Wagner & Pouya Kheradpour & Matthew L. Eaton & Paul Loriaux & Rachel Sealfon & Zirong Li & Haruh, 2011. "A cis-regulatory map of the Drosophila genome," Nature, Nature, vol. 471(7339), pages 527-531, March.
    5. Gemma Cadby & Corey Giles & Phillip E. Melton & Kevin Huynh & Natalie A. Mellett & Thy Duong & Anh Nguyen & Michelle Cinel & Alex Smith & Gavriel Olshansky & Tingting Wang & Marta Brozynska & Mike Ino, 2022. "Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    6. Ben C. Collins & Christie L. Hunter & Yansheng Liu & Birgit Schilling & George Rosenberger & Samuel L. Bader & Daniel W. Chan & Bradford W. Gibson & Anne-Claude Gingras & Jason M. Held & Mio Hirayama-, 2017. "Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiaofeng Liao & Wenxue Li & Hongyue Zhou & Barani Kumar Rajendran & Ao Li & Jingjing Ren & Yi Luan & David A. Calderwood & Benjamin Turk & Wenwen Tang & Yansheng Liu & Dianqing Wu, 2024. "The CUL5 E3 ligase complex negatively regulates central signaling pathways in CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Joe J. Lim & Christian Diener & James Wilson & Jacob J. Valenzuela & Nitin S. Baliga & Sean M. Gibbons, 2023. "Growth phase estimation for abundant bacterial populations sampled longitudinally from human stool metagenomes," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Jonathan P. Ling & Alexei M. Bygrave & Clayton P. Santiago & Rogger P. Carmen-Orozco & Vickie T. Trinh & Minzhong Yu & Yini Li & Ying Liu & Kyra D. Bowden & Leighton H. Duncan & Jeong Han & Kamil Tane, 2022. "Cell-specific regulation of gene expression using splicing-dependent frameshifting," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    4. Alina C. Teuscher & Cyril Statzer & Anita Goyala & Seraina A. Domenig & Ingmar Schoen & Max Hess & Alexander M. Hofer & Andrea Fossati & Viola Vogel & Orcun Goksel & Ruedi Aebersold & Collin Y. Ewald, 2024. "Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    5. Sandra M. Holmberg & Rachel H. Feeney & Vishnu Prasoodanan P.K. & Fabiola Puértolas-Balint & Dhirendra K. Singh & Supapit Wongkuna & Lotte Zandbergen & Hans Hauner & Beate Brandl & Anni I. Nieminen & , 2024. "The gut commensal Blautia maintains colonic mucus function under low-fiber consumption through secretion of short-chain fatty acids," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    6. Iris Chen & Yogeshwar D Kelkar & Yu Gu & Jie Zhou & Xing Qiu & Hulin Wu, 2017. "High-dimensional linear state space models for dynamic microbial interaction networks," PLOS ONE, Public Library of Science, vol. 12(11), pages 1-20, November.
    7. Hao Chen & Frederick J. King & Bin Zhou & Yu Wang & Carter J. Canedy & Joel Hayashi & Yang Zhong & Max W. Chang & Lars Pache & Julian L. Wong & Yong Jia & John Joslin & Tao Jiang & Christopher Benner , 2024. "Drug target prediction through deep learning functional representation of gene signatures," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Joanna F Dipnall & Julie A Pasco & Michael Berk & Lana J Williams & Seetal Dodd & Felice N Jacka & Denny Meyer, 2016. "Into the Bowels of Depression: Unravelling Medical Symptoms Associated with Depression by Applying Machine-Learning Techniques to a Community Based Population Sample," PLOS ONE, Public Library of Science, vol. 11(12), pages 1-19, December.
    9. Vinod Nikhra, 2019. "Therapeutic Potential of Gut Microbiome Manipulation: Concepts in Fecal Microbiota Transplantation," Current Research in Diabetes & Obesity Journal, Juniper Publishers Inc., vol. 11(1), pages 1-9, June.
    10. Ali Akbar Ashkarran & Hassan Gharibi & Elizabeth Voke & Markita P. Landry & Amir Ata Saei & Morteza Mahmoudi, 2022. "Measurements of heterogeneity in proteomics analysis of the nanoparticle protein corona across core facilities," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    11. Huimin Ye & Sabrina Borusak & Claudia Eberl & Julia Krasenbrink & Anna S. Weiss & Song-Can Chen & Buck T. Hanson & Bela Hausmann & Craig W. Herbold & Manuel Pristner & Benjamin Zwirzitz & Benedikt War, 2023. "Ecophysiology and interactions of a taurine-respiring bacterium in the mouse gut," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    12. Amanda H Pendegraft & Boyi Guo & Nengjun Yi, 2019. "Bayesian hierarchical negative binomial models for multivariable analyses with applications to human microbiome count data," PLOS ONE, Public Library of Science, vol. 14(8), pages 1-23, August.
    13. Robin D Couch & Allyson Dailey & Fatima Zaidi & Karl Navarro & Christopher B Forsyth & Ece Mutlu & Phillip A Engen & Ali Keshavarzian, 2015. "Alcohol Induced Alterations to the Human Fecal VOC Metabolome," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-24, March.
    14. Mika Saarenpää & Marja I. Roslund & Riikka Puhakka & Mira Grönroos & Anirudra Parajuli & Nan Hui & Noora Nurminen & Olli H. Laitinen & Heikki Hyöty & Ondrej Cinek & Aki Sinkkonen & the ADELE Research , 2021. "Do Rural Second Homes Shape Commensal Microbiota of Urban Dwellers? A Pilot Study among Urban Elderly in Finland," IJERPH, MDPI, vol. 18(7), pages 1-19, April.
    15. Alice Risely & Kerstin Wilhelm & Tim Clutton-Brock & Marta B. Manser & Simone Sommer, 2021. "Diurnal oscillations in gut bacterial load and composition eclipse seasonal and lifetime dynamics in wild meerkats," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    16. Narongrit Sritana & Atitaya Phungpinij, 2024. "Analysis of Oral Microbiota in Elderly Thai Patients with Alzheimer’s Disease and Mild Cognitive Impairment," IJERPH, MDPI, vol. 21(9), pages 1-15, September.
    17. Brian A. Hodge & Geoffrey T. Meyerhof & Subhash D. Katewa & Ting Lian & Charles Lau & Sudipta Bar & Nicole Y. Leung & Menglin Li & David Li-Kroeger & Simon Melov & Birgit Schilling & Craig Montell & P, 2022. "Dietary restriction and the transcription factor clock delay eye aging to extend lifespan in Drosophila Melanogaster," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    18. Milton Pividori & Sumei Lu & Binglan Li & Chun Su & Matthew E. Johnson & Wei-Qi Wei & Qiping Feng & Bahram Namjou & Krzysztof Kiryluk & Iftikhar J. Kullo & Yuan Luo & Blair D. Sullivan & Benjamin F. V, 2023. "Projecting genetic associations through gene expression patterns highlights disease etiology and drug mechanisms," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    19. Isabel Tundidor & Marta Seijo-Vila & Sandra Blasco-Benito & María Rubert-Hernández & Sandra Adámez & Clara Andradas & Sara Manzano & Isabel Álvarez-López & Cristina Sarasqueta & María Villa-Morales & , 2023. "Identification of fatty acid amide hydrolase as a metastasis suppressor in breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    20. Hania M. Taha & Alexander N. Slade & Betty Schwartz & Anna E. Arthur, 2022. "A Case–Control Study Examining the Association of Fiber, Fruit, and Vegetable Intake and the Risk of Colorectal Cancer in a Palestinian Population," IJERPH, MDPI, vol. 19(12), pages 1-11, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44343-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.