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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.

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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.

Keywords:
glycemic controlhyaluronanhymecromoneinsulin resistancelongevity

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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.