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Nature aging
09, 2022;2 (9): 824-836.

Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy.

Paula Juricic, Yu-Xuan Lu, Thomas Leech, Lisa F Drews, Jonathan Paulitz, Jiongming Lu, Tobias Nespital, Sina Azami, Jennifer C Regan, Emilie Funk, Jenny Fröhlich, Sebastian Grönke, Linda Partridge
Author Information
  1. Paula Juricic: Max Planck Institute for Biology of Ageing, Cologne, Germany.
  2. Yu-Xuan Lu: Max Planck Institute for Biology of Ageing, Cologne, Germany. ORCID
  3. Thomas Leech: Max Planck Institute for Biology of Ageing, Cologne, Germany.
  4. Lisa F Drews: Max Planck Institute for Biology of Ageing, Cologne, Germany.
  5. Jonathan Paulitz: Max Planck Institute for Biology of Ageing, Cologne, Germany.
  6. Jiongming Lu: Max Planck Institute for Biology of Ageing, Cologne, Germany. ORCID
  7. Tobias Nespital: Max Planck Institute for Biology of Ageing, Cologne, Germany.
  8. Sina Azami: Max Planck Institute for Biology of Ageing, Cologne, Germany. ORCID
  9. Jennifer C Regan: Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, London, UK. ORCID
  10. Emilie Funk: Max Planck Institute for Biology of Ageing, Cologne, Germany.
  11. Jenny Fröhlich: Max Planck Institute for Biology of Ageing, Cologne, Germany.
  12. Sebastian Grönke: Max Planck Institute for Biology of Ageing, Cologne, Germany. ORCID
  13. Linda Partridge: Max Planck Institute for Biology of Ageing, Cologne, Germany. linda.partridge@age.mpg.de. ORCID
PMID: 37118497 DOI: 10.1038/s43587-022-00278-w

Abstract

The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid adverse side effects from continuous dosing. Here we show that geroprotective effects of chronic rapamycin treatment can be obtained with a brief pulse of the drug in early adulthood in female Drosophila and mice. In Drosophila, a brief, early rapamycin treatment of adults extended lifespan and attenuated age-related decline in the intestine to the same degree as lifelong dosing. Lasting memory of earlier treatment was mediated by elevated autophagy in intestinal enterocytes, accompanied by increased levels of intestinal LManV and lysozyme. Brief elevation of autophagy in early adulthood itself induced a long-term increase in autophagy. In mice, a 3-month, early treatment also induced a memory effect, with maintenance similar to chronic treatment, of lysozyme distribution, Man2B1 level in intestinal crypts, Paneth cell architecture and gut barrier function, even 6 months after rapamycin was withdrawn.

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MeSH Term

Animals
Female
Mice
Sirolimus
Muramidase
Paneth Cells
Drosophila
Autophagy

Chemicals

Sirolimus
Muramidase
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 827

Word Cloud

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