Rafal Smigrodzki's Research into Mitochondria

Researcher Rafal Smigrodski was kind enough to post a preview of a forthcoming Rejuvenation Research paper to the ExI Chat List today:

A few months ago I promised to post an article on mitochondria and aging which I was writing with Shaharyar Khan, and finally I can keep my promise. "Mitochondrial microheteroplasmy and a theory of aging and age-related disease" will be published in Rejuvenation Research in August. Here is the text (without figures) and I can send the pdf to anyone interested.


We implicate a recently described form of mitochondrial mutation, mitochondrial microheteroplasmy, as a candidate for the principal component of aging. Microheteroplasmy is the presence of hundreds of independent mutations in one organism, with each mutation usually found in 1 - 2% of all mitochondrial genomes. Despite the low abundance of single mutations, the vast majority of mitochondrial genomes in all adults are mutated. This mutational burden includes inherited mutations, de novo germline mutations, as well as somatic mutations acquired either during early embryonic development or later in adult life. We postulate that microheteroplasmy is sufficient to explain the pathomechanism of several age-associated diseases, especially in conditions with known mitochondrial involvement, such as diabetes (DM), cardiovascular disease, Parkinson's disease (PD), and Alzheimer's disease (AD) and cancer. The genetic properties of microheteroplasmy reconcile the results of disease models (cybrids, hypermutable PolG variants and mitochondrial toxins), with the relatively low levels of maternal inheritance in the aforementioned diseases, and provide an explanation of their delayed, progressive course.

As long-time readers will be aware, Rafal has an enviable position with a research group focusing on mitochondria, working on important projects such as tools to manipulate and repair mitochondrial damage. While there is still a great deal of uncertainty in the relationship between mitochondria and aging (all the more reason for more funding), it is quite clear that this is a very promising avenue of research for healthy life extension. As I'm sure you know, repair of mitochondrial mutations is one of the seven pillars of Aubrey de Grey's Strategies for Engineered Negligible Senescence (SENS).


Then, if my understanding is correct, currently there are two items from the SENS strategy which are starting :
- the removal of accumulated extracellular junk (see post : More Medical Nanomachines, posted Wednesday June 15 )
- repair of mitochondrial mutations (current post).

Does some one know if there are any others items (from SENS strategy) which are covered (or starting) or does it remains 5 items to starts ?

Posted by: Carlo at June 17th, 2005 5:16 AM

The situation is a lot better than that, luckily. Work to remove extracellular junk and extracellular crosslinks is already in clinical trials, as are various therapies to reverse cell depletion (e.g. with stem cells). Work to remove superfluous cells (such as visceral fat) is well underway in mice, and various approaches to obviating or removing mitochondrial mutations are being pursued, of which Rafal's is the newest. So actually there are only two that are really still on the starting blocks - and one of them, removal of intracellular junk, is the subject of a variety of pilot studies just starting up, which I've been able to initiate in labs in the UK and USA.

See http://www.gen.cam.ac.uk/sens/just7.htm for more on the status of all these things.

Posted by: Aubrey de Grey at June 17th, 2005 4:34 PM

So which is the one that is not being worked on yet, and are there any plans to start work on it anytime soon?

Posted by: Josh Zmijewski at June 24th, 2005 9:29 PM
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