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

Nature Aging, ISSN: 2662-8465, Vol: 2, Issue: 9, Page: 824-836
2022
  • 50
    Citations
  • 0
    Usage
  • 109
    Captures
  • 134
    Mentions
  • 169
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    50
  • Captures
    109
  • Mentions
    134
    • News Mentions
      123
      • News
        123
    • References
      7
      • Wikipedia
        7
    • Blog Mentions
      4
      • Blog
        4
  • Social Media
    169
    • Shares, Likes & Comments
      169
      • Facebook
        169

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Article Description

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Man2B1 level in intestinal crypts, Paneth cell architecture and gut barrier function, even 6 months after rapamycin was withdrawn.

Bibliographic Details

Juricic, Paula; Lu, Yu-Xuan; Leech, Thomas; Drews, Lisa F; Paulitz, Jonathan; Lu, Jiongming; Nespital, Tobias; Azami, Sina; Regan, Jennifer C; Funk, Emilie; Fröhlich, Jenny; Grönke, Sebastian; Partridge, Linda

Springer Science and Business Media LLC

Neuroscience; Biochemistry, Genetics and Molecular Biology; Medicine

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