Looking for Metusaleh genes

Kiel scientists confirm conncection between genetic variants and longevity in humans

In their paper published in the scientific journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) on 5 February 2009, the Research Group for Healthy Ageing describes the connection between a sequence variation in the FOXO3A gene and longevity. In centenarians, this variant is conspicuously frequent.

The findings of Stefan Schreiber’s team at the Institute for Clinical Molecular Biology confirm the results of an earlier study by Bradley J. Wilcox, who thought FOXO3A a possible longevity gene after conducting a study with long-lived US Americans of Japanese descent.

Family and twin studies have shown that the capacity to reach a very old age is influenced by environmental factors (70%) and genetics (30%). In all probability, FOXO3A is only one of many genes that play a role in longevity. Apart from FOXO3A, so far only one other longevity gene could be found in different populations.

The scientists in Kiel have now proved a predisposition for healthy ageing in German centenarians with the FOXO3A variation. Their French project partner, the Centre d’Etude du Polymorphisme Humain CEPH, with whom they co-operate closely, found the same trend in French centenarians.

The Kiel researchers analysed more than 380 DNA samples of individuals 100 years of age and older. This demanding study could only be conducted with the support of the popgen biobank whose staff is constantly looking for long-lived individuals older than 98 years.

The Research Group for Healthy Ageing is supported by the Cluster of Excellence "Inflammation at Interfaces".

Selected articles regarding this topic are provided below.

DFG funding for the identification and characterization of functional variants in the FOXO3A gene

In order to affect the human ageing process advantageously in the future , it is necessary to understand the molecular mechanisms that have a positive effect on health. That is why the next goal is now to examine which the causative gene variants in the FOXO3A gene that cause a long and healthy life are and which effects they trigger in the human body.

For this purpose, financial support has been granted by the “Deutsche Forschungsgemeinschaft” (DFG). For the detection of so far unknown genetic variants, FOXO3A is being subjected to an intensive examination by re-sequencing (Sanger and Next Generation Sequencing) of the whole gene. The potential functional influence of all identified polymorphisms (rare and frequent ones) is subsequently tested by in silico analysis.

The gene variants of interest are then tested for the longevity phenotype by analyzing them in a cohort of approx. 1400 long-lived German individuals and approx. 1100 younger controls. The associated variants are further functionally characterized by different in vitro and ex vivo experiments. The identification of variants relevant for ageing will provide important insights into the FOXO3A mediated molecular mechanisms that lead to healthy longevity in humans.

Funding period: 7/2010 – 6/2013

Funding: The project has been funded by the Deutsche Forschungsgemeinschaft DFG as an individual grant.