The SENS Approach to Mitochondrial Damage in Aging
It is always good to more respectful attention given to the Strategies for Engineered Negligible Senescence (SENS) approach to rejuvenation treatments. Rendering us immune to mitochondrial DNA damage and its consequences is just one of a number of future therapies that will be needed to reverse all of the underlying causes of aging, but in and of itself this is perhaps the most technically interesting of the biotechnologies adopted and advocated by SENS:
In this fast-paced talk by Dr. Aubrey de Grey, we hear about a breathtakingly radical approach to forestalling aging, which (in a nutshell) involves moving all remaining mitochondrial genes into the nuclear DNA, so that mutations in mitochondrial DNA, per se, are rendered irrelevant. This technique of "obviation" of mitochondrial-DNA breakdown isn't a new idea (it's been around for at least 30 years). What's new is that, technologically, we're in a position to make it happen.Most mitochondrial genes are, of course, already in the nucleus. The majority of scientists accept that mitochondria got their start as bacterial endosymbionts; a long-ago ancestor of today's alphaproteobacteria took up residency in an anaerobe. The anaerobe provided the invading bacterium with a nutrient-rich environment in which to live, while the bacterium provided oxygen-detoxification services (and a lot of adenosine triphosphate) to the host. Most likely, the invading bacterium had around 1,500 genes. Over time, ~500 redundant genes were lost and the remaining 1,000 or so migrated to the host cell's nuclear DNA (a much safer environment for DNA than the mitochondrion), leading to the present-day situation where (human) mitochondria have an extremely small circular chromosome encoding just 13 proteins. But we know mitochondria actually contain around 1,000 different proteins, most of which are encoded in nuclear genes.
The majority of mitochondrial genes (in the nucleus) encode proteins that are made in cytoplasm and imported into the mitochondrion. For import, proteins must be in an unfolded state. Some proteins (the most hydrophobic ones) are actually made on the surface of the mitochondrion and slurped into the interior of the mitochondrion as they're being made. Folding of the proteins then takes place inside the organelle.
Can the remaining 13 mitochondrial protein genes be moved to the nucleus? If we succeed in doing that, will cells live longer? What technical obstacles remain? What progress has been made? These and other questions are addressed in Aubrey de Grey's talk, which is well worth a listen.
Link: http://asserttrue.blogspot.com/2014/06/a-different-approach-to-anti-aging.html
It is a very good question if this can be done, as some have suggested there might be reasons why those genes haven't been moved. But another interesting question is is this necessary for greater lifespan?
Neurons are said to be metabolically similar in cost across mammalian species. Soon we will have the bowhead genome, if this mammal manages 200+year high metabolism neuron lifespan and its genome does not show such transference of genes from mitochondria to nucleus, it will suggest that there are likely easier alternatives to preserving mitochondrial quality through time.