Mitochondria in homeotherm aging: will detailed mechanisms consistent with the evidence now receive attention?

It is exceptionally gratifying to see someone with the authority of Irwin Fridovich stating (Fridovich, 2004) so emphatically in a leading biogerontology journal what mitochondriologists have been telling gerontologists for well over a decade, viz. that only ∼ 0.1% of electrons are 'fumbled' by the mammalian respiratory chain in normal circumstances. The perpetuation of the higher estimate in so many papers is not a testament to the attention paid by either authors or peer reviewers to the data being cited; let us hope that it will now decline. What is less gratifying, in some ways, is to see the bulk of a special issue on the mitochondrial theory of aging dedicated to a dissection of the shortcomings of simplistic, early versions of that theory that no one who respects the data has propounded for ages. The idea that the respiratory chain might become inherently dysfunctional with age is, as is so clearly stated here, absolutely at odds with what we know. A mitochondrial theory of aging consistent with available data must thus be more sophisticated, as are the three such hypotheses put forward in back-to-back papers in Eur. J. Biochem. two years ago by myself, Aiken's group and Brunk's group (Brunk & Terman, 2002; de Grey, 2002; McKenzie et al ., 2002). It is most unfortunate that so many of those who consider mitochondria to be important in aging ignore this, thereby distracting the critics of mitochon-drial theories into basing entire articles on outdated premises, such as that 'The mitochondrial theory of aging is based around the idea of a vicious cycle, in which somatic mutation of mtDNA engenders respiratory chain dysfunction, enhancing the production of DNA-damaging oxygen radicals' (Jacobs, 2003). Therefore, it is in reality appropriate to regard Aging Cell 3 (1) as an important step forward for mitochondrial theories of aging, in that it may silence those who are still wedded to early ideas such as the vicious cycle theory, thereby promoting discussion and experimental testing of refined models that are entirely consistent with presently available data, in contrast to the current tendency to dismiss those models as 'exotic' and 'desperate' (Jacobs, 2003) or not to discuss them at all. As in any field, what is exotic to the non-specialist is merely sophisticated to the specialist, however, 'objective' the non-specialist may think he is being. I speak as one who jumped to the corresponding erroneous conclusion regarding the …