Research has revealed two rare coding variants in the IGF-1 gene that might contribute to longevity.
Scientists conducted whole-exome sequencing on over 2,100 individuals, including centenarians, their descendants, and a comparison group, aiming to identify variants in the IGF-1 gene linked to extended lifespan.
The study, published in Scientific Reports, highlights two likely functional variants: IGF-1:p.Ile91Leu and IGF-1:p.Ala118Thr. Notably, the IGF-1:p.Ile91Leu variant, found specifically in centenarians, is located at the binding interface of IGF-1 and its receptor (IGF-1R). Meanwhile, IGF-1:p.Ala118Thr is associated with lower circulating levels of IGF-1 and may affect the overall function of the insulin-like growth factor signaling pathway.
Researchers utilized advanced molecular dynamics simulations to examine how these variants influence the stability and dynamics of IGF-1 when bound to IGF-1R. Results indicated that the IGF-1:p.Ile91Leu variant demonstrated significantly less stability in its interactions with critical binding residues compared to the wild-type IGF-1.
Furthermore, carriers of these variants remained healthy, free from diabetes or cardiovascular diseases, indicating potential pathways for healthy aging. The data support the existing hypothesis that reduced IGF-1 signaling can contribute to longevity by diminishing growth-promoting effects and enhancing resilience against age-related diseases.
This study not only adds to the understanding of genetic factors influencing human longevity but also opens avenues for future research that may help define gerotherapeutic approaches and improve healthspan among aging populations.
Such findings might provide insights into the molecular mechanisms underlying exceptional longevity, shedding light on the biology of aging and disease resistance.
