Functionally significant insulin-like growth factor I receptor mutations in centenarians.
Level 4 - case-series / case-control
Case-control genetic association and biomarker study with in vitro functional follow-up
PubMed 18316725 · doi:10.1073/pnas.0705467105
What was done
The authors evaluated biochemical, phenotypic, and genetic characteristics in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched control subjects. They sequenced the IGF1 and IGF1 receptor (IGF1R) genes in female centenarians and controls and measured IGF-1R functional activity in transformed lymphocytes.
What was found
The abstract reports no exact numerical values or effect sizes. Qualitatively, female offspring of centenarians exhibited a gender-specific increase in serum IGF-I associated with shorter stature. Sequence analysis revealed an overrepresentation of heterozygous IGF1R mutations among female centenarians compared to controls, which correlated with higher serum IGF-I levels and reduced IGF-1R signaling activity in transformed lymphocytes.
Why it matters
This study provides genetic and biochemical evidence that evolutionary conserved down-regulation of the IGF-I signaling pathway may contribute to exceptional longevity in humans.
Limits
The abstract omits sample sizes, mutation frequencies, effect sizes, and statistical confidence intervals. The study was conducted exclusively in an Ashkenazi Jewish founder population, and key findings were restricted to females, limiting generalizability to other populations and to males. Functional validation relied on in vitro lymphocyte assays rather than direct in vivo physiologic measurements.
Cited by
- supports Genetic polymorphisms in the IGF-1 receptor and FOXO genes are associated with human longevity.