The aging brain, metals and oxygen free radicals

In this overview we bring together certain facts and concepts that support the theory that the aging of "disease-free" brain is a consequence of the a ccumulated cellular-molecular modifications caused by oxygen free radicals. The relevance of transition metals, especially iron ions, in the productio n of oxygen free radicals, initiation of oxidative chain-reactions and in s ite-specific molecular modifications is documented. Mitochondria are identi fied as the major source of oxygen free radicals, and mitochondrial DNA is a likely target. Special attention is given to iron-sulfur clusters as sour ces of reactive iron and sites of modifications. Potential mechanisms by wh ich oxygen free radicals can alter membrane receptors and intracellular sig naling are cited. Although the evidence is still correlative, the oxygen fr ee radical theory has strong experimental support and has promise for facil itating a better understanding of the "disease-free", aging brain.