Gene

IGF1R

Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

Why this gene matters

The DAF-2 (insulin/IGF-1 receptor) longevity-extension principle in C. elegans generalises to mammals. Mice with heterozygous IGF1R knockout have extended female lifespan. Suh and colleagues showed that Ashkenazi centenarians carry functionally-significant heterozygous IGF1R mutations more often than expected.

This is a rare instance where the worm-to-human longevity translation is direct and mechanistic.

Effects

Reduced IGF1R signalling produces:

Lower IGF-1 effect at target cells.
Reduced PI3K/AKT/mTOR activation.
Maintained FOXO3 nuclear localisation.
Likely reduced cancer incidence over the lifespan.

What this implies

Therapeutic IGF-1R antagonism is in oncology development (rejecting cancer cells’ growth-factor signal) but generally not used for longevity.
Diet/lifestyle interventions that lower IGF-1 (protein restriction, caloric restriction) likely mimic some of the centenarian-genotype effect.
The narrow therapeutic window matters: very low IGF-1 in older adults promotes frailty.

References

Suh, Y. et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc. Natl. Acad. Sci. USA 105, 3438–3442 (2008).