SENS5 Video: Gene Therapy for Mitochondrial Repair

We age in part because a small number of important genes in our mitochondria are broken over time by the polluting effects of their day to day operation: broken genes mean the protein machines produced from their blueprints are also broken, or cannot be produced at all. Mitochondria are bacteria adapted to act as the power plants for our cells, swarms of them circulating inside every cell - and perversely the broken ones tend to win out in the ongoing, dynamic process of replication, damage control, and recycling of cellular machinery that takes place inside all of our cells. Cells can become overtaken by broken mitochondria, each herd of malfunctioning power plants spawned from one original chance breakage, and enough of these unfortunate cells produce a chain of unpleasant consequences throughout the body. Aging is damage, after all. This is a long story, and a better introduction than this can be found back in the archives, however.

SENS stands for the Strategies for Engineered Negligible Senescence, a detailed proposal for what must be done at the cellular and molecular level to reverse the damage of aging and thereby rejuvenate the old. SENS-related research is to vary degrees conducted in labs around the world, and where the research community isn't already large and hard at work - such as in the field of regenerative medicine - the SENS Foundation organizes and encourages research programs. One of the earliest SENS programs to move from concept to actual research, starting back when the initiative was conducted by the Methuselah Foundation, is MitoSENS: a way to use biotechnology to prevent mitochondrial damage from contributing to degenerative aging.

Mitochondrial genes are distinct from those in the nucleus of a cell, and as such are vulnerable. The available repair mechanisms are not as good as those in the nucleus, and the genes in each mitochondrion are right next door to power plant machinery that sustains the cell but also kicks out damaging reactive molecules. The MitoSENS strategy is twofold: (a) gene therapy to copy the few important mitochondrial genes into the cell nucleus, known as allotopic expression, and (b) one of a range of clever biotechnological strategies to get the protein machinery produced from those gene blueprints from the nucleus back out to the mitochondria where it is needed. You might look at the work of Corral-Debrinsky's group to see this in action in a real research program: when you have nuclear copies of mitochondrial genes, it doesn't matter if the more vulnerable mitochondrial versions suffer mishaps, everything continues as before.

A further good introduction to this topic and the work of the SENS Foundation is spurring this research can be found in video recorded at the recent SENS5 conference. Conference videos are being posted to the SENS Foundation YouTube channel as they are processed, and here is an educational presentation on the state of allotopic expression of mitochondrial genes:


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