Mechanisms of ageing and senescence
- A new vertebrate model organism to study life span determinants (Nothobranchius project)
The identification of vertebrate genes that control ageing is hampered by the relatively long life span of most animal models. We have chosen a novel vertebrate model, a species of annual fish, Nothobranchius furzeri, with a genetically determined short life span. In addition, Nothobranchius furzeri represents an ideal model system to investigate means of life-extension. Several aspects are pursued: genome analysis for life span markers, study of gene expression in relation to ageing, genetic manipulation of the genome to validate candidate genes for ageing. A first-generation linkage map of the Nothobranchius furzeri genome is being constructed (Cellerino, Englert, Platzer).
- Genetic determinants of healthy ageing
Human life expectancy is influenced by environmental, genetic and epigenetic factors. Approximately 30% of the variation in life span is attributable to genetic constitution. Epidemiological studies have revealed that individuals who survive to exceptional age show a favorable course of the ageing process with absence or delayed onset of age-associated diseases. Discovering interindividual genetic variants that modulate life expectancy may yield important insights into mechanisms both of healthy ageing as well as age-related disease susceptibility. Exploiting one of the worldwide largest DNA collections of centenarians, a large-scale candidate gene association study with longevity (University Kiel) has yielded a number of candidate genes. We focus on: (i) gene structure and transcript identification (Platzer), (ii) the effect of genetic variations on expression and epigenetic marks (Platzer), (iii) the Nothobranchius furzeri screens of small molecular compounds as potential modulators of healthy ageing (Cellerino).