IGF1R

insulin-like growth factor 1 receptor

Gene Information

Gene Symbol

IGF1R

Aliases

JTK13, CD221, IGFIR, MGC18216, IGFR

HGNC ID

HGNC:5465

NCBI Gene ID

3480

Ensembl Gene ID

ENSG00000140443

Gene Type

protein coding

Genomic Location

Chromosome

Assembly

GRCh38

Start Position

98,648,539

End Position

98,964,530

Number of Exons

Gene Length

315,992 bp

Overview

The receptor for IGF1, IGF1R, mediates the activation of the IGF1-stimulated signalling cascade. Evidence from model organisms, including results from flies and roundworms, relates IGF1R homologues to ageing, most likely as part of the GH1/IGF1 axis. Mice (129/SvPas genetic background) heterozygous for IGF1R live 26% longer, though it is unclear whether they age slower. Null mutants are not viable. In the B6 genetic background however, IGF-1R+/- female mutants show only an 11% lifespan extension, while males do not show any changes in median lifespan and have a slightly shorter maximum lifespan. In male mice where IGF1R has been knocked out specifically in cardiomyocytes, cardiac ageing is attenuated. Fibrosis and expression of proinflammatory cytokines and NFKB1 are reduced when compared to wild type mice. IGF1R integrates nutrient and temperature homeostasis in mice and a reduction in IGF1R enhances the reduction of temperature and energy expenditure seen during calorie restriction. Therefore, IGF1 signalling plays a role in regulating hypothermia during calorie restriction. The IGF1/GH1 axis appears to impact on ageing in model organisms, including rodents, and so IGF1R may affect human ageing. In humans, IGF1R has been implicated with growth retardation, and genotype combinations in the human IGF1R and PIK3CB genes have been related to plasma IGF1 levels and longevity.

Research Papers

19 papers in databaseSearch for More Papers

Score:

90%

Development of an IGF1R longevity variant mouse line using CRISPR/Cas9 genome editing.

Trends Biomed Res

2020

PMID: 37113577

Modification Effects

IGF1R variant (Arg407His) in exon 6; reduced IGF1R activity and decreased IGF1R phosphorylation

Longevity Association

Extended health span and median lifespan in progeroid Ercc1 (-/Delta) mice; potential for increased longevity in Igf1r hR407H variant mice, model organism: mice

Score:

90%

Identification of functional rare coding variants in IGF-1 gene in humans with exceptional longevity.

Sci Rep

2025

PMID: 40133344

Modification Effects

IGF-1:p.Ile91Leu and IGF-1:p.Ala118Thr variants; impaired IGF-1 binding to IGF-1R and reduced circulating IGF-1 levels

Longevity Association

Exceptional longevity in humans; mechanism: diminished IGF-1 signaling through impaired binding and reduced circulatory levels

Score:

90%

Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death.

Aging Cell

2010

PMID: 20409077

Modification Effects

Increased dosage of p44, a short isoform of the p53 gene; hyperactivation of IGF-1R signaling and altered tau metabolism

Longevity Association

Accelerated aging, premature death, and neurodegeneration in mice; mechanism: altered IGF-1R signaling, paraptosis- and autophagy-like cell deaths

Score:

90%

Suppression of IGF-I signals in neural stem cells enhances neurogenesis and olfactory function during aging.

Aging Cell

2015

PMID: 26219530

Modification Effects

IGF-1R knockout in neural stem cells; increased neuroblast production, enhanced neuronal integration, and altered energy metabolism

Longevity Association

Improved olfactory function and neurogenesis during aging in mice; mechanism: diminished IGF-I signaling, altered Akt and ERK pathways

Score:

80%

Progerin modulates the IGF-1R/Akt signaling involved in aging.

Sci Adv

2022

PMID: 35857466

Modification Effects

LMNA mutation leads to progerin production; progerin mislocalizes, interacts with IGF-1R, and down-regulates its expression

Longevity Association

Premature aging in HGPS patients and Zmpste24(-/-) mice; mechanism: impaired IGF-1R/Akt signaling, inhibited mitochondrial respiration, and accelerated cellular senescence

Score:

80%

Decreased IGF1R attenuates senescence and improves function in pancreatic beta-cells.

Front Endocrinol (Lausanne)

2023

PMID: 37441495

Modification Effects

Decreased IGF1R expression; improved glucose-induced insulin secretion, increased transcription of Mafa, Nkx6.1, and Kcnj11, decreased senescence-related genes

Longevity Association

Suppressed cellular senescence, improved beta-cell function and identity; mechanism: reduced IGF1R signaling, enhanced autophagy and mTOR signaling in mouse beta-cells

Score:

80%

Rapid molecular evolution across amniotes of the IIS/TOR network.

Proc Natl Acad Sci U S A

2015

PMID: 25991861

Modification Effects

Divergent evolutionary rates of IIS/TOR network components, including IRS and PI3K, between reptiles and mammals; positively selected sites on IGF1, IGF1R, INSR in reptiles and IGF2 in mammals

Score:

80%

Targeting IGF1R signaling for brain aging and Alzheimer's disease.

Aging Pathobiol Ther

2022

PMID: 36776414

Modification Effects

IGF1R R407H variant; reduced IGF1R protein activity

Longevity Association

Improved cognitive performance in middle-aged mice; potential therapeutic target for Alzheimer's disease and brain aging

Score:

80%

The age of heterozygosity.

Age (Dordr)

2006

PMID: 19943141

Modification Effects

Igf1r (+/-) and mclk1 (+/-) mutations; reduced insulin-like growth factor-1 signaling and ubiquinone biosynthesis

Longevity Association

Significantly increased lifespan in mice; mechanism: reduced insulin/IGF-1 signaling and altered ubiquinone biosynthesis, observed in Igf1r (+/-) and mclk1 (+/-) models

#10

Score:

80%

The genetic component of human longevity: New insights from the analysis of pathway-based SNP-SNP interactions.

Aging Cell

2018

PMID: 29577582

Longevity Association

Synergic interactions of SNPs in IIS, DNA repair, and pro/antioxidant pathways; significant effect on longevity for GHSR gene and combinations (e.g., IGF1R-rs12437963 and PTPN1-rs6067484); improved survival in nonagenarian females

#11

Score:

80%

Longevity effect of IGF-1R(+/-) mutation depends on genetic background-specific receptor activation.

Aging Cell

2014

PMID: 23898955

Modification Effects

IGF-1R(+/-) mutation; reduced IGF-1R activation and altered insulin/IGF signaling

Longevity Association

Lifespan extension in female mice; strain-dependent effect with greater extension in 129/SvPas (significant) than C57BL/6J background; mechanism involves reduced oxidative stress and altered GH/IGF signaling

#12

Score:

80%

Arrestin and the multi-PDZ domain-containing protein MPZ-1 interact with phosphatase and tensin homolog (PTEN) and regulate Caenorhabditis elegans longevity.

J Biol Chem

2010

PMID: 20207731

Modification Effects

ARR-1 C-terminal PDZ binding domain interacts with MPZ-1; regulates DAF-2 signaling

Longevity Association

Increased longevity in arr-1 mutant C. elegans; decreased longevity with ARR-1 overexpression; mechanism: regulation of DAF-2 signaling and insulin-like growth factor receptor pathway

#13

Score:

80%

Local cannabinoid receptor type-1 regulates glial cell activity and insulin-like growth factor-1 receptor signaling in the mediobasal hypothalamus.

Mech Ageing Dev

2024

PMID: 38821184

Modification Effects

CB1 receptor deletion; increased pro-inflammatory glial activity and Igf1r mRNA expression, CB1 receptor re-expression; reduced pro-inflammatory glial activation and decreased Igf1r mRNA expression

Longevity Association

Reduced age-related inflammation and modulation of IGF-1R signaling in mice; mechanism: CB1 receptor regulation in the mediobasal hypothalamus

#14

Score:

80%

Silencing circATXN1 in Aging Nucleus Pulposus Cell Alleviates Intervertebral Disc Degeneration via Correcting Progerin Mislocalization.

Research (Wash D C)

2024

PMID: 38533181

Modification Effects

CircATXN1 silencing; reduced progerin mislocalization, up-regulation of IGF-1R, and improved mitochondrial function

Longevity Association

Delayed intervertebral disc degeneration in progerin pathologically expressed premature aging mice (zmpste24(-/-)); mechanism: reduced cellular senescence, improved mitochondrial respiration, and corrected progerin localization

#15

Score:

80%

Blocking IGF Signaling in Adult Neurons Alleviates Alzheimer's Disease Pathology through Amyloid-beta Clearance.

J Neurosci

2015

PMID: 26290229

Modification Effects

IGF-1R knock-out in adult neurons; reduced amyloid-beta accumulation, altered neuronal structure (leaner dendrites, reduced apical soma), and enhanced autophagic compartment

Longevity Association

Delayed Alzheimer's disease progression in mice; mechanism: enhanced amyloid-beta clearance, reduced neuroinflammation, and improved proteostasis

#16

Score:

80%

Growth Hormone Receptor Deficiency Protects against Age-Related NLRP3 Inflammasome Activation and Immune Senescence.

Cell Rep

2016

PMID: 26876170

Modification Effects

Growth Hormone Receptor (GH-R) deficiency; downregulation of NLRP3 inflammasome in macrophages, increased preservation of naive T cells

Longevity Association

Pro-longevity effects, maintenance of immune system homeostasis, increased health span and longevity in mice; mechanism: inhibition of NLRP3-mediated innate immune signaling, reduced chronic inflammation

#17

Score:

80%

Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

PLoS Biol

2008

PMID: 18959478

Modification Effects

Partial inactivation of brain IGF-1R; inhibited GH and IGF-I pathways, growth retardation, metabolic alterations

Longevity Association

Delayed mortality, longer mean lifespan in mice; mechanism: adaptive plasticity of somatotropic functions, preserved resources

#18

Score:

80%

Association of IGF1R polymorphisms (rs1546713) with susceptibility to age-related cataract in a Han Chinese population.

Int J Ophthalmol

2020

PMID: 32309172

Modification Effects

IGF1R polymorphism (rs1546713); altered cell proliferation, cell cycle arrest, and apoptosis regulation

Longevity Association

Increased susceptibility to age-related cataract in Han Chinese population; mechanism: disrupted cell cycle progression and enhanced apoptosis

#19

Score:

60%

Genetic variation in healthy oldest-old.

PLoS One

2009

PMID: 19680556

Longevity Association

Prolonged lifespan in healthy oldest-old humans; mechanism: possibly enhanced disease resistance and lack of disease susceptibility factors

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