Somatroph axis (GH) and its relationship to dietary restriction and aging (WP4186)

Homo sapiens

The somatotrophic axis in mammals comprises the growth hormone (GH), which is produced by the anterior pituitary, and its secondary mediator, insulin-like growth factor 1 (IGF-1). The intracellular signaling pathway of IGF-1 is the same as that elicited by insulin, which informs cells of the presence of glucose. For this reason, IGF-1 and insulin signaling are known as the insulin and IGF-1 signaling (IIS) pathway. Remarkably, the IIS pathway is the most conserved aging-controlling pathway in evolution, and among its multiple targets are the FOXO family of transcription factors and the mTOR complexes, which are also involved in aging and conserved through evolution. Genetic polymorphisms or mutations that reduce the functions of GH, IGF-1 receptor, insulin receptor, or downstream intracellular effectors such as AKT, mTOR, and FOXO have been linked to longevity. Molecules that favor aging are shown in orange, and molecules with anti-aging properties are shown in light green. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal].


Rik Lahaije , Denise Slenter , Andra Waagmeester , Kristina Hanspers , and Egon Willighagen


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Homo sapiens



Pathway Ontology

growth factor signaling pathway aging pathway


Label Type Compact URI Comment
GH Metabolite chebi:37845
FOXO GeneProduct ensembl:ENSG00000150907
IGF-1 GeneProduct ensembl:ENSG00000140443
SIRT1 GeneProduct ensembl:ENSG00000096717
MTOR GeneProduct ensembl:ENSG00000198793
AKT GeneProduct ensembl:ENSG00000142208
PTEN Protein ensembl:ENSG00000171862
PI3K Protein ncbiprotein:NP_006209.2
PGC-1 alpha Protein uniprot:Q01711
AMPK Protein eccode:


  1. The hallmarks of aging. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Cell. 2013 Jun 6;153(6):1194–217. PubMed Europe PMC Scholia