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Probing the relationship between insulin sensitivity and longevity using genetically modified mice.

James F Nelson1, Randy Strong, Alex Bokov

  • 1Department of Physiology, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, Texas 78245, USA. nelsonj@uthscsa.edu

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
|October 24, 2012
PubMed
Summary
This summary is machine-generated.

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Altering insulin signaling impacts mouse lifespan. Reduced insulin sensitivity extended lifespan in male mice, while increased sensitivity shortened it, suggesting an inverse relationship between insulin sensitivity and longevity.

Area of Science:

  • Genetics
  • Aging Research
  • Metabolic Disease

Background:

  • Insulin and insulin-like growth factor 1 (IGF-1) signaling pathways are known to influence lifespan in invertebrates and mice.
  • The role of interfering with murine insulin signaling in longevity remains controversial due to potential diabetogenic and pathological effects.

Purpose of the Study:

  • To investigate the relationship between insulin sensitivity and lifespan in genetically modified mouse models.
  • To determine if reduced or increased insulin sensitivity affects murine longevity.

Main Methods:

  • Assessed lifespan in three mouse strains: insulin receptor knockout (IRKO(+/-)) for reduced sensitivity, PTP-1B knockout (PTP-1B(-/-)) and PGC-1α overexpression (PGC-1α(TG)) for increased sensitivity.
  • Compared survival rates across genotypes.

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Main Results:

  • Insulin-insensitive IRKO(+/-) mice showed increased lifespan in males and unaffected lifespan in females.
  • Mice with increased insulin sensitivity (PTP-1B(-/-) and PGC-1α(TG)) exhibited shortened lifespans overall or partially.
  • Demonstrated an inverse correlation between insulin sensitivity and longevity in specific murine genotypes.

Conclusions:

  • Insulin sensitivity is inversely related to longevity in certain mouse genotypes.
  • These findings support the conserved role of insulin signaling as a modulator of lifespan across species.