Proposing Synthetic Mitochondria as a Treatment for Aging
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Mitochondria are the power plants of the cell, generating chemical energy stores used in many cellular processes. A herd of them exists in every cell, dividing like bacteria to keep up their numbers. Mitochondrial damage occurs as a side-effect of the normal operation of metabolism and is an important contribution to degenerative aging, but fortunately there are a wide range of fairly well understood methods by which this issue could be prevented or treated. All that is needed is more funding for research and development.

One possibility is the delivery of replacement mitochondria, and if doing this why not deliver better, more effective mitochondria? Some of the existing mitochondrial haplogroups are objectively better than others, but we could also in theory greatly improve upon what exists based on present knowledge. At the end of this road lies the replacement of mitochondria with optimal synthetic versions, resistant to damage, which influence surrounding cellular mechanisms in beneficial ways, and which minimize the mitochondrial contribution to aging. That isn't a near term prospect, but in the decades ahead it will become very plausible to start replacing more discrete cellular components with designed molecular machinery that is more efficient and less vulnerable, and thus helps to extend healthy life span:

We hypothesize herein that synthetic mitochondria, engineered or reprogrammed to be more energetically efficient and to have mildly elevated levels of reactive oxygen species (ROS) production, would be an effective form of therapeutics against systemic aging. The free radical and mitochondria theories of aging hold that mitochondria-generated ROS underlies chronic organelle, cell and tissues damages that contribute to systemic aging. More recent findings, however, collectively suggest that while acute and massive ROS generation during events such as tissue injury is indeed detrimental, subacute stresses and chronic elevation in ROS production may instead induce a state of mitochondrial hormesis (or "mitohormesis") that could extend lifespan.

Mitohormesis appears to be a convergent mechanism for several known anti-aging signaling pathways. Importantly, mitohormetic signaling could also occur in a non-cell autonomous manner, with its induction in neurons affecting gut cells, for example. Technologies are outlined that could lead towards testing of the hypothesis, which include genetic and epigenetic engineering of the mitochondria, as well as intercellular transfer of mitochondria from transplanted helper cells to target tissues.

Link: http://dx.doi.org/10.1002/cbin.10362

Comments

What's the current state of the art of wholescale mitochondrion replacement?

I wonder if a short term improvement might be to let evolution do the work for us - put current mitochondria in an artificially stressful environment, and see if we can't evolve improved versions even if we don't understand exactly how the improvements might work.

Posted by: Dennis Towne at September 5, 2014 2:50 PM

Seems silly. Mitochondria renew in a process of fission/fusion. Parts of broken mitochondria are linked together in fusion and then separated into new regenerated mitochondria with fission. This fission/fusion process is accelerated by resveratrol and probably other polyphenols. I think it would be implausible to think of replacing hundreds of mitochondria in every cell of the body (where would you begin to inject the synthetic mitochondria?). Mitochondrial regeneration has been demonstrated and is the more practical way to go.

Posted by: Bill Sardi at September 7, 2014 10:07 AM

In response to the previous comment: The problem with relying on mitochondrial biogenesis and mitophagy indefinitely is that it is imperfect in its ability to maintain fidelity. Mitochondrial DNA mutation can and will occur. While some of these mutations will be detected and repaired, eventually others will evade detection. Upregulating mitobiogenesis beyond its natural slowed state in aged organisms will likely result in accelerated spread of mitochondrial mutants and inflict more damage than it repairs.

Posted by: Brett Augsburger at September 8, 2014 11:04 AM

I think mitochondria only escape mitophagy if they stop respiring. Clonal expansion and survivial of the slowest, it's all in the book there.

Posted by: Michael-2 at September 9, 2014 1:42 AM
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