Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans.
Level 3 - non-randomized controlled study
Prospective 22-year non-randomized cohort study with relative controls and in vitro mechanistic assays.
PubMed 21325617 · doi:10.1126/scitranslmed.3001845
What was done
Researchers followed an Ecuadorian cohort carrying growth hormone receptor (GHR) gene mutations causing severe GHR and insulin-like growth factor-1 (IGF-1) deficiency for 22 years, combined with historical surveys of deceased community members. Clinical prevalence of cancer and diabetes, fasting insulin levels, and homeostatic model assessment of insulin resistance (HOMA-IR) were compared against unaffected relatives and controls. In vitro assays evaluated the effects of serum from GHR-deficient subjects on hydrogen peroxide-treated human mammary epithelial cells, assessing DNA breaks, apoptosis, and signaling pathways (RAS, PKA, TOR, SOD2).
What was found
Individuals with GHR deficiency developed 1 nonlethal malignancy and 0 cases of diabetes, compared to a prevalence of 17% for cancer and 5% for diabetes in control subjects. GHR-deficient subjects had lower insulin concentrations (1.4 μU/ml vs. 4.4 μU/ml in unaffected relatives) and a lower HOMA-IR index (0.34 vs. 0.96). In cell culture, serum from GHR-deficient subjects reduced DNA breaks, increased apoptosis upon hydrogen peroxide exposure, downregulated RAS, PKA, and TOR expression, and upregulated SOD2 expression.
Why it matters
This study provides human genetic evidence that congenital disruption of the GH/IGF-1 signaling axis protects against major age-related diseases, specifically cancer and diabetes, mirroring longevity pathways observed in model organisms.
Limits
The abstract does not state the total sample size (n) or exact statistical confidence intervals. The findings are based on a specific, genetically isolated Ecuadorian population with rare mutations, which may not directly generalize to the broader human population, and some historical data relied on retrospective surveys.
Cited by
- supports Individuals in Ecuador with growth hormone receptor deficiency (Laron syndrome) are protected from cancer, diabetes, and age-dependent cognitive decline.
- supports Human epithelial cells exposed to serum from individuals with Laron syndrome exhibit downregulation of TOR and Ras gene expression compared to cells exposed to control serum.