Mitochondrial Rejuvenation Via Induced Pluripotency Techniques?

I noticed a very interesting open access paper today, a good example of the sort of barnstorming experimentation in stem cell science that is taking place now that near-every laboratory can create pluripotent stem cells easily and at low cost. In essence the researchers did the following:

It's more complicated than that, of course, and the researchers add a list of caveats as long as your arm in the discussion - they don't have a full understanding of what is happening here and why. Their summary:

We have examined the properties of mitochondria in two fibroblast lines, corresponding IPSCs, and fibroblasts re-derived from IPSCs using biochemical methods and electron microscopy, and found a dramatic improvement in the quality and function of the mitochondrial complement of the re-derived fibroblasts compared to input fibroblasts. This observation likely stems from two aspects of our experimental design: 1) that the input cell lines used were of advanced cellular age and contained an inefficient mitochondrial complement, and 2) the re-derived fibroblasts were produced using an extensive differentiation regimen that may more closely mimic the degree of growth and maturation found in a developing mammal.

Lack of understanding aside, there is clearly something interesting going on. If there is a mechanism there to be exploited, perhaps it may be usefully applied to the development of stem cell therapies for the aged. One of the big potential issues with the whole field of tissue engineering and stem cell medicine is that old people have old stem cells and old biochemistries: damaged, dysfunctional, and problematic. But at the same time, old people are those who need these therapies the most. Therefore we want to know that there are ways to include the repair of cellular damage in any potential stem cell therapy or tissue engineering project - an extra step in between taking the source cells from the patient and then returning the modified therapeutic cells.

As regular readers might recall, one of the many aspects of an aged biochemistry is that the mitochondria, the swarming power plants of the cell, are damaged and dysfunctional to some degree. This accumulating mitochondrial damage is in fact one of the causes of aging, and the short explanation as to why it happens is that the cell's recycling mechanism cannot properly identify and destroy certain forms of damaged mitochondria. So it is interesting to see a process demonstrated - even a fairly radical process - whereby a cell can reset its mitochondria to a fully functional state.

Like a number of the things I point out here at Fight Aging!, I think this has no direct and immediate application to the reversal of aging. You can't revert and re-differentiate all your cells, or at least not if you want to continue living. For repair of mitochondria throughout the body, you should be looking in the direction of protofection research, or the mitoSENS project - or anything else mentioned in the summary of mitochondrial repair research posted earlier this year. But that said, it is very encouraging for the future of tissue engineering and regenerative medicine to see this sort of cell rejuvenation demonstrated. It is beginning to seem as though the hurdles imposed by an age-damaged biochemistry might not be so great after all - see this report from earlier in the year, for example:

"Regardless of the gender or age of the patient, or of diabetes, we were able to isolate in all of them a pool of functional cardiac stem cells that we can potentially use to rescue the decompensated human heart."

This is good news as well as expected, since I'm convinced that the aging process is rooted exclusively in the mitochondria.

Posted by: kurt9 at December 4th, 2010 10:48 AM

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