An Update on Leishmania and Mitochondrial DNA Repair
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The ability to repair accumulated damage to our mitochondrial DNA is one necessary item in the rejuvenation biotechnology toolkit of the future. You can look back in the Fight Aging! archives to see why this the case, but the short version is that your mitochondria damage their DNA as a natural consequence of their operation, and this damage is the start of a chain of events that ultimately spreads harm and dysfunction throughout the body. Mitochondrial DNA damage is thus one of the causes of aging.

Fortunately, there are a number of promising avenues for repair technologies. One of the newer approaches involves adopting a mechanism observed in the tropical parasite Leishmania:

Dr. Samit Adhya of the Division of Molecular and Human Genetics at the Indian Institute of Chemical Biology is pursuing yet another innovative approach. He proposes to dispense with the need for mitochondrial DNA altogether, by instead providing the mitochondrial protein-making machinery directly with the "working instructions" (messenger RNA) that it normally receives in the form of a transcribed copy taken from the mitochondrial DNA originals. This would allow the mitochondria to continue their protein production even if the mitochondrial DNA were completely destroyed: they would still have their marching orders, even if the general himself were incommunicado. Dr. Adhya is accomplishing this goal by borrowing a trick used by a single-celled organism called Leishmania tropica. This organism, unlike mammals, generates another kind of RNA in the main cell body, and uses a specialized protein to move it into the mitochondria. Dr. Adhya reasoned that he could bind copies of our own RNA to the same protein and use it to deliver both kinds of RNA into mammalian mitochondria, bypassing the need for a DNA original. Very clever.

Over at the SENS Foundation - a group working on a different methodology of making mitochondrial damage irrelevant - you'll find an update on development of this Leishmania-derived mechanism. The article is fairly dense, but the gist of it is that Samit Adhya and company took mutant cells with massively broken mitochondrial DNA and temporarily fixed their operation by providing them with doses of RNA tailored to create the protein components that their damaged DNA couldn't produce. From the commentary:

This in vitro experiment is exciting, opening up an alternative means of restoring [necessary mitochondrial function to] cells that accumulate in aging tissues, areas associated with age-related diseases such as Parkinson's disease and sarcopenia, and that can strongly be argued to be contributors to the degenerative aging process. The method is rightly described by the authors as "inherently simple, efficient, and fast-acting, and appears to be of general applicability to a wide variety of [cells and tissues]." Indeed, it shows clear advantages relative to the low targeting to cells and/or mitochondria of previous attempts using pharmacological delivery systems, and appears to show a [greater effectiveness] than previous efforts using allotopic expression itself.

On the other hand, the effects of the [RNA based therapy were] transient, as would be predicted from the inherent nature of a therapy based on delivery of mRNA, which are routinely recycled within the cell ... there is substantial room for skepticism that normal function could be continuously sustained by such means on acceptable booster schedules.

But this work is a major advance, and clearly promising. The therapeutic potential [should] now be tested in animal models of inherited mitochondrial disease, [and] if successful, the more ambitious work of using it to restore [cells become damaged] as a result of the degenerative aging of wild-type mice. The biomedical rejuvenation of aging human mitochondrial function would not lie far behind, with the promise of muscles maintained, Parkinson's prevented, and an end to the rising systemic metabolic toxicity of [cells overrun with damaged mitochondria].

The more methods of mitochondrial repair that are actively worked on the better the long-term prognosis for all of us - though it should be noted that despite progress over the past few years, there is comparatively little funding for this field of research and development. Few groups are working in this area, and in comparison to hot fields like stem cell research, progress is slow and halting. The cure for that problem is as it always has been: funding, attention, advocacy.

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