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

James F Nelson, John R Strong, Alex Bokov, Vivian Diaz, Walter Ward

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Interference in insulin and/or insulin-like growth factor 1 (IGF-1) signaling can extend invertebrate life span, and interference in IGF-1 signaling can extend murine life span. Whether interference with murine insulin signaling, which can be diabetogenic and pathological, is also life-extending is controversial. We therefore measured life span in 3 murine strains genetically modified to reduce or increase insulin sensitivity. Mice with reduced insulin sensitivity were hemizygous for a null mutation in the insulin receptor (insulin receptor knockout mice; IRKO/-). Mice with increased insulin sensitivity either had a null mutation of protein tyrosine phosphatase 1B (PTP-1B-/-) or overexpressed Peroxisome proliferator-activated receptor-α coactivator (PGC)-1α (PGC-1αTG). Life span of insulin insensitive IRKO/ mice was increased (males) or unaffected (females). Life spans of mice with increased insulin sensitivity were shortened overall (PTP-1B-/- mice) or partially (PGC- 1αTG: survival at the 25th percentile was reduced). These results show that insulin sensitivity in some murine genotypes is inversely related to longevity and provide further evidence for evolutionary conservation of this pathway as a modulator of longevity.

Original languageEnglish (US)
Pages (from-to)1332-1338
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume67
Issue number12
DOIs
StatePublished - Dec 2012

Fingerprint

Insulin Resistance
Non-Receptor Type 1 Protein Tyrosine Phosphatase
Insulin Receptor
Somatomedins
Insulin
Mutation
Peroxisome Proliferator-Activated Receptors
Invertebrates
Knockout Mice
Genotype

Keywords

  • Insulin sensitivity
  • Life span
  • Longevity
  • Mice.

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Probing the relationship between insulin sensitivity and longevity using genetically modified mice. / Nelson, James F; Strong, John R; Bokov, Alex; Diaz, Vivian; Ward, Walter.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 67, No. 12, 12.2012, p. 1332-1338.

Research output: Contribution to journalArticle

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