Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

By V. Katuri, A. Dillner, Bibhuti Mishra, Chu-Xia Deng, Lopa Mishra. Science, 2003

1,382 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/7a71871f918069198b7eb4e81754a692333aeef0

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

In Physiology

Citations in the corpus

Calorie restriction and aging: review of the literature and implications for studies in humans. (2003, background): “Indeed, fat-specific insulin receptor knockout mice, which have normal or even increased food intake and reduced adiposity, have increased median and maximal life expectancies (132).”
Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans (2003, background): “In wild-type animals, the activity of DAF-16 is inhibited by a conserved phosphatidylinositol-3-OH kinase (PI(3)K)/protein kinase D (PDK)/Akt pathway in response to DAF-2 activity(1).”
Sirt1 Regulates Insulin Secretion by Repressing UCP2 in Pancreatic β Cells (2005, positive): “The paucity of fat in WAT appears to be sufficient per se to promote a degree of longevity, since mice engineered for leanness—for example, a WAT-specific knockout (KO) of the insulin receptor—live longer [6,7].”
Insulin Action in Brain Regulates Systemic Metabolism and Brain Function (2014, background): “However, fat-specific IR knockout mice (119) and whole-body IGF1R heterozygous mice (120) both have an extended median and maximum life span (;15–20%).”
FOXO transcription factors at the interface between longevity and tumor suppression (2005, background): “FOXO factors are pivotal downstream targets of the insulin/IGF-1 pathway and mice that are deficient for either the insulin receptor or the IGF-1 receptor are long lived and resistant to oxidative stress stimuli (Bluher et al., 2003; Holzenberger et al., 2003).”
Reversal of obesity by targeted ablation of adipose tissue (2004, result): “Consistent with our results, recent studies in mice lacking PTP1B or the fat-specific insulin receptor demonstrated that low body fat can be maintained, despite normal food intake, without detectable side effect”
Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. (2003, background): “Our tissue-specific ex- the insulin receptor in adipose tissue, are also long-lived pression, mosaic analysis, and RNAi experiments each (Blüher et al., 2003).”
Growth Hormone Receptor Deficiency is Associated With a Major Reduction in Pro-aging Signaling, Cancer and Diabetes in Humans (2011, neutral): “In this case however, loss of insulin signaling is restricted to adipose tissue and is not associated with diabetes or glucose intolerance (75).”
How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis). (2010, background): “In addition, adipocyte-specific disruption of the insulin receptor extends murine life span (Blüher et al., 2003) and so does global heterozygous disruption of the downstream insulin receptor substrate 1 (IRS-1) (Selman et al., 2008a) which interestingly also is located downstream of the of IGF-1…”
Life and death: metabolic rate, membrane composition, and life span of animals. (2007, neutral): “elegans (103, 172), Drosophila (62, 350), and mice (30, 149).”
FOXO3A genotype is strongly associated with human longevity (2008, background): “For example, mice with a fat-specific insulin receptor knockout (FIRKO) have reduced fat mass, protected against age-related obesity, and have extended longevity (21).”
Calorie restriction, SIRT1 and metabolism: understanding longevity (2005, background): “Indeed, tissue-specific knockout of the insulin receptor in WAT prevents the tissue from storing fat, which gives rise to lean animals that live significantly longer than wild-type mic”