The discovery of a new mutation that causes an unusually severe form of a disease that results in accelerated ageing (progeria), may help to reconcile two seemingly disparate theories of ageing.
Some think that ageing is genetically regulated; others, that it is due to a gradual build up of cellular damage. In Nature, Jan H. J. Hoeijmakers and colleagues suggest that both theories are correct and provide firm evidence that specifically DNA damage contributes to ageing.
The team discovered a new mutation in the XPF gene of a human patient that causes a dramatic form of progeria. Young mice that have been genetically engineered to model this syndrome show many features of normal old mice. These include reduced insulin signalling; increased cell death, increased cellular defense mechanisms; and a shift towards anabolism - the building up of new tissues. The results suggest that an accumulation of DNA damage induces metabollic changes aimed at extending life rather than maintaining growth.
They conclude that DNA damage contributes to the functional decline associated with ageing. But genetics, and in particular the insulin signalling pathway and cellular defense systems, influence how rapidly damage accumulates and function is lost.
Jan H. J. Hoeijmakers (Erasmus MC, Rotterdam, The Netherlands)
Tom Kirkwood (Newcastle University, UK) News & Views author
(C) Nature press release.
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