SENS Foundation on Recent Mitochondrial Research

The SENS Foundation here comments on recent research that may make it easier to build therapies to treat mitochondrial DNA damage in order to remove its contribution to aging: "The UCLA group's approach is highly promising. Their work builds upon and may potentially supersede several previous approaches to the problem of mitochondrial mutations that occur as a result of the degenerative aging process, including allotopic protein expression, its optimization using [a mitochondrial targeting sequence], and the exploitation of the multiprotein RNA import complex (RIC) of the protozoal parasite Leishmania tropica (which the investigators characterize as 'requir[ing] the introduction of nonnative tRNAs with foreign protein factors or the transfer of a large multisubunit aggregate into cells, which is of low efficiency and difficult to reproduce in desirable disease-relevant settings' ... As compared to allotopic protein expression, an RNA-based approach has the theoretical advantage of abrogating the difficulties encountered thus far with the mitochondrial import of large and hydrophobic proteins. But as we suggested in discussion of their earlier, more discovery-phase research, allotopic protein and RNA approaches are not mutually exclusive: different mitochondrially-encoded proteins could be either allotopically expressed, or their mRNAs generated allopically and imported for in situ translation, depending on the ease or efficiency of each approach for the protein in question. ... For their part, Dr. Teitell's group is evidently optimistic, and have clearly moved beyond the basic science focus of their earlier report. ... In response to this report, SENS Foundation CSO Dr. Aubrey de Grey has said that 'If this is as good as it looks, I think it could be a real game-changer', and Dr. O'Connor and his team at the SENS Foundation RC are considering testing a construct based on Teitell's methods in a system that the RC has already generated and used for testing of allotopic expression of cytochrome B. The race is on -- as it should be, for the stakes are large. Large, age-related deletions in mtDNA are likely responsible for the systemic rise in oxidative stress with aging, and for localized but terrible pathologies of skeletal muscle and substantia nigra dopaminergic neurons in aging bodies. The obviation of these mutations is a desperate medical need, and biomedicine is shamed for every day that a solution is delayed. This new method must be tested and exploited to its limits, and all approaches must be trialed, until the fires of life are once again burning in rejuvenated cells, in bodies restored to their youthful prime."

Link: http://www.sens.org/node/2682