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Accumulation of F-actin drives brain aging and limits healthspan in Drosophila

Author

Listed:
  • Edward T. Schmid

    (University of California, Los Angeles)

  • Joseph M. Schinaman

    (University of California, Los Angeles)

  • Naomi Liu-Abramowicz

    (University of California, Los Angeles)

  • Kylie S. Williams

    (University of California, Los Angeles)

  • David W. Walker

    (University of California, Los Angeles
    University of California, Los Angeles)

Abstract

The actin cytoskeleton is a key determinant of cell structure and homeostasis. However, possible tissue-specific changes to actin dynamics during aging, notably brain aging, are not understood. Here, we show that there is an age-related increase in filamentous actin (F-actin) in Drosophila brains, which is counteracted by prolongevity interventions. Critically, decreasing F-actin levels in aging neurons prevents age-onset cognitive decline and extends organismal healthspan. Mechanistically, we show that autophagy, a recycling process required for neuronal homeostasis, is disabled upon actin dysregulation in the aged brain. Remarkably, disrupting actin polymerization in aged animals with cytoskeletal drugs restores brain autophagy to youthful levels and reverses cellular hallmarks of brain aging. Finally, reducing F-actin levels in aging neurons slows brain aging and promotes healthspan in an autophagy-dependent manner. Our data identify excess actin polymerization as a hallmark of brain aging, which can be targeted to reverse brain aging phenotypes and prolong healthspan.

Suggested Citation

  • Edward T. Schmid & Joseph M. Schinaman & Naomi Liu-Abramowicz & Kylie S. Williams & David W. Walker, 2024. "Accumulation of F-actin drives brain aging and limits healthspan in Drosophila," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53389-w
    DOI: 10.1038/s41467-024-53389-w
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    1. Po-Lin Chen & Kai-Ting Huang & Chu-Ya Cheng & Jian-Chiuan Li & Hsiao-Yen Chan & Tzu-Yang Lin & Matthew P. Su & Wei-Yuan Yang & Henry C. Chang & Horng-Dar Wang & Chun-Hong Chen, 2020. "Vesicular transport mediates the uptake of cytoplasmic proteins into mitochondria in Drosophila melanogaster," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    2. Cierra N. Sing & Enrique J. Garcia & Thomas G. Lipkin & Thomas M. Huckaba & Catherine A. Tsang & Arielle C. Coughlin & Emily J. Yang & Istvan R. Boldogh & Ryo Higuchi-Sanabria & Liza A. Pon, 2022. "Identification of a modulator of the actin cytoskeleton, mitochondria, nutrient metabolism and lifespan in yeast," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Simon C. Johnson & Peter S. Rabinovitch & Matt Kaeberlein, 2013. "mTOR is a key modulator of ageing and age-related disease," Nature, Nature, vol. 493(7432), pages 338-345, January.
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