Editors' ChoiceAging

DNA damage linked to fitness loss in aging

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Science  09 Jun 2017:
Vol. 356, Issue 6342, pp. 1041
DOI: 10.1126/science.356.6342.1041-a

Inhibiting a DNA-repair kinase improves physical fitness in old mice.


Loss of metabolic function is associated with physical decline and diseases associated with aging. Park et al. provide evidence for a link between accumulated DNA damage and such metabolic dysfunction. Activity of the DNA-dependent protein kinase (DNA-PK), which is activated in response to DNA damage, was increased in skeletal muscle of older mice. DNA-PK phosphorylates HSP90α, a chaperone protein that protects the activity of a key metabolic regulator called adenosine monophosphate–activated protein kinase. A small-molecule inhibitor of DNA-PK improved the physical fitness of young obese mice and older mice. Whether such benefits can be provided without the deleterious effects of inhibited DNA repair, such as cancer, remains to be explored.

Cell Metab. 10.1016/j.cmet.2017.04.022 (2017).

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