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Acarbose improved survival for Apc+/Min mice.

Sherry G Dodds1, Manish Parihar1, Martin Javors2

  • 1Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health, San Antonio, TX, USA.

Aging Cell
|January 7, 2020
PubMed
Summary

Acarbose extended lifespan in mice by improving carbohydrate metabolism, not by suppressing cancer. This suggests metabolic health is key for longevity.

Keywords:
acarbosecancerlongevitypolyposis

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Area of Science:

  • Gerontology and Metabolic Health
  • Cancer Biology and Prevention

Background:

  • Acarbose demonstrated lifespan extension in mice (NIA ITP), but the mechanism (metabolism vs. cancer suppression) remained unclear.
  • Cancer was the primary cause of death (~80%) in ITP mice.
  • Rapamycin, an mTORC1 inhibitor, extended survival and suppressed tumors in Apc+/Min mice, suggesting a potential parallel for acarbose.

Purpose of the Study:

  • To investigate whether acarbose suppresses intestinal tumors and extends lifespan in Apc+/Min mice, a model for familial adenomatous polyposis.
  • To determine if acarbose's lifespan-extending effects are linked to cancer suppression or improvements in metabolic health.

Main Methods:

  • Apic+/Min mice were fed two doses of acarbose.
  • Median survival was assessed.
  • A cross-sectional analysis evaluated intestinal crypt depth, weight, food consumption, blood glucose, plasma insulin, and liver AMPK/mTORC1 activity.

Main Results:

  • Acarbose significantly improved median survival at both doses.
  • Mice receiving acarbose showed reduced intestinal crypt depth, weight loss, decreased postprandial blood glucose and insulin, indicating improved insulin sensitivity.
  • High-dose acarbose reduced tumor number and increased hematocrit; low-dose acarbose improved lifespan without reducing tumors.

Conclusions:

  • Acarbose extends lifespan in Apc+/Min mice, with effects appearing independent of cancer suppression at lower doses.
  • Improved carbohydrate metabolism and insulin sensitivity are implicated as key drivers of acarbose-mediated lifespan extension.
  • These findings highlight the critical role of metabolic health in promoting longevity.