Acarbose improved survival for Apc^+/Min mice.

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.