Long life and short stature share common genetic link

Researchers at the Yeshiva University in New York have uncovered a genetic variant that appears to confer both a long-life and short stature to its female carriers. The study, published in Proceedings of the National Academy of Sciences, found mutations in the insulin-like growth factor (IGF1) receptor gene that appear to restrict cell growth but extend human longevity.

Dubbed the 'Methuselah' gene, after the biblical legend, the IGF1 gene and the pathway within which it operates have been cited before as one of the key determinants of lifespan. With minor manipulation of the pathway in roundworms, researchers saw a reduction in body size and a 30-50 per cent increase in lifespan. The study has since been replicated in mice with similar results.

The current work attempted to show that the effect translates to humans by screening genes from the IGF1 pathway in 450 Ashkenazi (Eastern European) Jews aged between 95 and 110 years old - looking for coding errors. The scientists identified mutations in the IGF-1 receptor genes in a greater proportion of female centenarians compared to the normal population, interestingly carriers were also 2.5cm below average population height - even in their prime.

Researchers say the IGF1 hormone is produced as normal in the individuals but their bodies are unable to process it efficiently. IGF-1's normal function within the body is as a driver of growth and maturity, a malfunctioning IGF-1 pathway will slow this process down. In fact, the body was apparently attempting to compensate for the lack of responsiveness by making yet more hormone: levels of IGF1 were on average 35 per cent higher in the blood of subjects with IGF1 receptor mutations. The same effect was seen in daughters of the centenarians, who also showed an increase in IGF1 production and a below average height.

'This milestone result will no doubt stimulate a worldwide search for IGF1 mutations in other centenarian populations', said Martin Holzenberger, a longevity researcher at Inserm in St Antoine, France.