Genetic mutation sheds new light on ageing process
The tragic case of a 15 year old boy struck with a genetic mutation, which caused him to age and die prematurely, has helped an international team of researchers shed new light on the ageing process. While many scientists believe ageing is genetically regulated, others think it is due to a gradual build up of cellular damage. This new study, which is partly funded by the EU, reconciles these two viewpoints. It is published in the latest edition of the journal Nature. There are a number of 'progeroid' syndromes, in which sufferers undergo rapid, premature ageing. Many of these are caused by defects in the cellular response to DNA damage. Study of these can help researchers to better understand the aging process. This new study arose after the discovery of a 15 year old boy who had frequent sunburn and a unique combination of ageing symptoms, indicating major damage to the boy's nucleotide excision repair (NER) system, which normally fixes damaged DNA. Genetic analysis revealed a mutation which affected production of an enzyme called XPF-ERCC1 endonuclease, which vital to the DNA repair process. The doctors named the new condition XFE progeroid syndrome. Further studies on mice with a similar mutation found that their symptoms were shared in large part by normal old mice. These included reduced insulin signalling, increased cell death and the build up of new tissues. The researchers suggest that as we age, damage to our DNA, for example as a result of exposure to toxins, accumulates. This DNA damage triggers metabolic changes, for example in the insulin system, which are designed to prolong life. 'This model reconciles two apparently disparate hypotheses of ageing: that ageing is genetically regulated and that ageing is a consequence of the accumulation of stochastic damage,' the authors conclude. 'In fact, both are correct. Damage drives the functional decline that is associated with aging; however, a highly conserved longevity assurance mechanism [...] influences how rapidly damage accumulates and function is lost.'