Longevity Pathway

Preferred Label : Longevity Pathway;

NCIt related terms : The IGF-1 Receptor and Longevity;

Alternative definition : BIOCARTA: A demonstrated means to increase lifespan in a wide range of organisms is through the restriction of caloric intake. Reducing the consumption of calories increases the lifespan of many different organisms, including mice. Caloric restriction not only increases lifespan, but decreases age-related deterioration of systems and physiological responses, reducing age related diseases like cancer and neurodegenerative disease. Although caloric restriction has not been demonstrated experimentally to increase human lifespan, short-term changes in physiological measures like insulin responsiveness have been observed. Caloric restriction in animals reduces the levels of plasma glucose and insulin and reduces inflammatory responses and may reduce oxidative stress through reduced oxidative metabolism, further contributing to the health benefits of reduced calorie intake. The reduction in inflammation may be related to reduced plasma glucose and in humans could reduce an inflammation connection to cancer, heart disease, and Alzheimer's disease. Genetic analysis has indicated several genes that influence lifespan, particularly those that alter pituitary development, reduce growth hormone secretion, reduce food intake, and reduce apoptosis (p66 Shc). All of these appear to converge on an IGF-1 receptor pathway and to reproduce many of the effects of caloric restriction. Although dwarf mice with defective growth hormone or IGF-1 signaling also have significantly increased lifespan, humans with defects in growth hormone signaling tend to develop diseases that shorten their lifespan. One of the downstream actions of IGF-1 signaling is to repress stress resistance proteins including antioxidant enzymes like superoxide dismutase and heat shock proteins, so a reduction in IGF signaling may extend lifespan by increasing the expression of stress resistance genes. The link between caloric restriction and IGF signaling may be the increased expression of stress resistance proteins. In addition to the IGF-1R mutation, p66 Shc mutation also increases lifespan without significant aberration of other systems. Shc is a target of IGF-1R phosphorylation, and a major inducer of cellular responses to oxidative stress. Shc increases levels of intracellular reactive oxygen species, repressing the forkhead factor FKHRL1. Although FKHRL1 is also involved in apoptosis, in the absence of Shc, FKHRL1 mediates increased resistance to oxidative stress. Exploration of the genes that induce longevity in animal models may enlighten the role of these genes in human disease and lifespan. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_longevityPathway;

Details

Origin ID

C39141;

UMLS CUI

C1517941;

Semantic type(s)
- Organism Function [UMLS semantic type]
has_gene_product_element
- 3-Phosphoinositide-Dependent Protein Kinase 1 [NCIt concept]
- Forkhead Box Protein O3 [NCIt concept]
- GTPase HRas [NCIt concept]
- Insulin Receptor Substrate 4 [NCIt concept]
- Insulin-Like Growth Factor 1 Receptor [NCIt concept]
- Insulin-Like Growth Factor I [NCIt concept]
- Phosphatidylinositol 3-Kinase Regulatory Subunit Alpha [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha Isoform [NCIt concept]
- Phosphatidylinositol 4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma Isoform [NCIt concept]
- RAC-Alpha Serine/Threonine Kinase [NCIt concept]
- SHC-Transforming Protein 1 [NCIt concept]
- Sestrin-1 [NCIt concept]
- Sestrin-3 [NCIt concept]
- Somatotropin [NCIt concept]
- Son of Sevenless Homolog 1 [NCIt concept]
- Superoxide Dismutase [Cu-Zn] [NCIt concept]
- Superoxide Dismutase [Mn], Mitochondrial [NCIt concept]
pathway_has_gene_element
- AKT1 wt Allele [NCIt concept]
- FOXO3 wt Allele [NCIt concept]
- GH1 wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- IGF1 wt Allele [NCIt concept]
- IGF1R wt Allele [NCIt concept]
- IRS4 wt Allele [NCIt concept]
- PDPK1 wt Allele [NCIt concept]
- PIK3CA wt Allele [NCIt concept]
- PIK3CG wt Allele [NCIt concept]
- PIK3R1 wt Allele [NCIt concept]
- SESN1 wt Allele [NCIt concept]
- SESN3 wt Allele [NCIt concept]
- SHC1 wt Allele [NCIt concept]
- SOD1 wt Allele [NCIt concept]
- SOD2 wt Allele [NCIt concept]
- SOS1 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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