Aging of the Other Genome: A Decisive but Ambitious Solution

Google Tech Talks December, 19 2007 The DNA in our cells consists of not only the well-known 46 chromosomes currently receiving such avid attention from specialists in sequencing technology, but also a large number of copies of a relatively tiny, circular DNA molecule inside the "powerhouse of the cell," the mitochondrion. Among other things, mitochondria perform the chemistry of breathing - they extract energy from nutrients by exquisitely regulated chemical reactions that consume oxygen and create CO2. This vital function depends on the 13 proteins encoded by the mitochondrial DNA (mtDNA), as well as on hundreds of proteins that are encoded in our more famous genome and imported across the mitochondrial surface after construction in the body of the cell. The mtDNA accumulates mutant, non-functional variants far faster than our main genome, so 20 years ago scientists began looking at the idea of putting copies of the 13 genes of interest into the nucleus after making modifications that would cause them to be processed by the same "protein import" machinery that processes the mitochondrion's many other proteins, thus making the mtDNA itself superfluous and mutations in it harmless. I will discuss this concept in detail in my talk. Progress has been very erratic in the meantime but is now very rapid, partly because of Methuselah Foundation-funded research. However, this approach may still prove impossible, so many other, ostensibly simpler ideas - some more promising than others - have been proposed, and I will describe some of these too. Speaker: Dr Aubrey de Grey Aubrey de Grey is a biomedical gerontologist based in Cambridge, UK, and is the Chairman and Chief Science Officer of the Methuselah Foundation, a 501(c)(3) non-profit charity dedicated to combating the aging process. He is also Editor-in-Chief of "Rejuvenation Research", the world's only peer-reviewed journal focused on intervention in aging. His research interests encompass the etiology of all the accumulating and eventually pathogenic molecular and cellular side-effects of metabolism ("damage") that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. He has developed a possibly comprehensive plan for such repair, termed Strategies for Engineered Negligible Senescence (SENS), which breaks the aging problem down into seven major classes of damage and identifies detailed approaches to addressing each one. A key aspect of SENS is that it can potentially extend healthy lifespan without limit, even though these repair processes will never be perfect, as the repair only needs to approach perfection rapidly enough to keep the overall level of damage below pathogenic levels. de Grey has termed this required rate of improvement of repair therapies "longevity escape velocity".