Key to longevity in the rodent world
Cellular resistance to stress, including resistance to oxidative stress, is thought to play a role in ageing and cancer. Stress resistance may also be a major biomarker for longevity in mammals. The 'Identification and functional characterization of genes associated with cellular biomarkers of longevity' (LONGENES) project has employed cutting edge genomics to identify new mammalian genes that confer genotoxic stress resistance. The scientists studied relevant candidate genes from the naked mole rat, Heterocephalus glaber, the granddaddy of all rodents, in comparison to short-lived mice. Using RNA interference techniques to silence genes involved in stress resistance, the scientists identified candidate RNA molecules and genes. They developed a novel method to detect short-hairpin RNA with subtle effects. Screening revealed genes for prioritisation. The researchers developed a bioinformatics pipeline for this purpose. Genes of particular interest include Edd1 and C1orf112. These affect cell proliferation as well as DNA damage responses when silenced, key processes required to maintain cell integrity. In parallel, interesting genes were cloned and sequenced. Gene analysis revealed several functional changes that may be associated with exceptional longevity. Key processes and genes are associated with mitochondria and oxidation reduction pathways. The LONGENES project developed the Naked Mole-Rat Genome Resource, the leading online mole rat facilities for study of the rodent genome. Research results have identified new genomic material and processes to study ageing. Applications for the future may well include treatment of age-related diseases.
Keywords
Naked mole rat, gene, longevity, genotoxic stress resistance, RNA interference, sequence, genome, age-related disease
