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Hymecromone Promotes Longevity and Insulin Sensitivity in Mice
Nadine Nagy1, Kathryn S Czepiel1, Gernot Kaber1
1Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University, Stanford, CA 94305, USA.
Cells
|October 25, 2024
Summary
The compound 4-methylumbelliferone (4-MU) significantly extended median survival and maximum lifespan in mice. This longevity effect was associated with improved insulin sensitivity and altered energy expenditure.
Area of Science:
- Gerontology and Metabolism
- Pharmacology
Background:
- Extracellular matrix hyaluronan (HA) is linked to longevity.
- 4-methylumbelliferone (4-MU) is an inhibitor of HA synthesis.
Purpose of the Study:
- To investigate the impact of long-term 4-MU administration on mouse lifespan.
- To explore the effects of 4-MU on metabolic parameters related to aging.
Main Methods:
- Prospective study involving long-term oral administration of 4-MU in C57BL/6J mice.
- Assessment of median and maximum lifespan.
- Evaluation of insulin sensitivity using insulin tolerance tests (ITT) and frequent sampling intravenous glucose tolerance tests (FSIVGTTs).
- Monitoring of food intake, body weight, and energy expenditure.
Main Results:
- 4-MU significantly increased median survival from 122 to 154 weeks (p < 0.0001).
- Maximum lifespan extended from 159 to 194 weeks in 4-MU treated mice.
- Enhanced insulin sensitivity and reduced body weight with unchanged food intake were observed.
- No significant changes in tissue HA content were detected.
Conclusions:
- 4-MU promotes insulin sensitivity and extends lifespan in mice.
- The precise mechanism of action, including the role of HA, remains unclear.
- 4-MU's metabolic effects suggest potential therapeutic benefits for longevity and chronic inflammatory conditions.
