Fight Aging!

Our mitochondria are responsible for a goodly portion of degenerative aging. Mitochondria are the power plants of the cell, responsible for building the chemical energy stores used to power cellular operations. Each mitochondrion is basically a wrapper membrane that encloses a fluid bag of protein machines, and every cell has a swarm of them floating around inside it. Mitochondria are the evolved descendants of symbiotic bacteria, and they still act much like bacteria in many ways: multiplying by division and promiscuously swapping protein machinery with one another, for example. They also have their own DNA, separate from the DNA in the cell nucleus, that encodes many of the proteins vital to their operation.

This DNA is where the problems start. It's sitting right next door to a power plant that generates all sorts of reactive byproducts - and so mitochondrial DNA is far more prone to harmful mutations than the DNA in the cell nucleus. The DNA repair mechanisms for mitochondria are worse as well.

Now in the case of most significant mitochondrial DNA damage caused this way, the damaged mitochondrion will eventually be broken down, destroyed by the cell's quality control mechanisms, and replaced through fission of a working mitochondrion. Unfortunately there are certain forms of damage that subvert the cell's ability to detect the resulting faulty operation of the mitochondrion - so it is left alone, to divide and create more faulty mitochondria. Once that happens, a cell is doomed to be overtaken by broken mitochondria and then fall into a maladaptive state of operation that exports harmful, reactive compounds into surrounding tissue.

With enough of that going on, real harm starts to accrue to organs and biological systems in the body: i.e. a part of why you become aged is because a small but significant portion of your cells are filled with broken mitochondria, and as a consequence are acting badly and causing damage. Aging is nothing more than an accumulation of damage, after all.

All of this is why research into ways to repair, replace, or otherwise deal with damaged mitochondria is so important. The research community is on the verge of being able to achieve these goals, and any resulting therapy will likely have a large impact on human aging - it will be a concrete step towards rejuvenation of the old, providing a way to remove this one signification contribution to degenerative aging.

Yesterday I was pointed towards some exciting research results in which scientists demonstrate that cells will ingest and adopt appropriately engineered mitochondria, adding them to the existing herd without the need for any intervention beyond placing the engineered mitochondria into the same cell culture. The researchers are calling their process peptide-mediated mitochondrial delivery:

Functional Recovery of Human Cells [via] Peptide-Mediated Mitochondrial Delivery

We explored the feasibility of mitochondrial therapy using the cell-penetrating peptide Pep-1 to transfer mitochondrial DNA (mtDNA) between cells ... Pep-1-conjugated wild-type mitochondria isolated from parent cybrid cells incorporating a mitochondria-specific tag were used as donors for mitochondrial delivery ... Forty-eight hours later, translocation of Pep-1-labelled mitochondria into the mitochondrial regions of [host] cells was observed (delivery efficiencies of 77.48 and 82.96%, respectively). These internalized mitochondria were maintained for at least 15 days in both cell types and were accompanied by mitochondrial function recovery

As you can imagine, this immediately leads one to think in terms of an infusion-type therapy, where a fluid solution containing hordes of mitochondria can be introduced into tissues and be taken up into cells. The mitochondria themselves can be cultivated like bacteria from a sample from the patient, which is gene engineered to fix issues such as genetic diseases caused by mutations in mitochondrial DNA - or they can be from a donor.

In a more liberated, free-wheeling future, this sort of approach might be widely used to swap out the mitochondria you are born with for a better set. It is already the case that some mitochondrial lineages have been shown to be better than others in terms of functionality and durability. Looking further ahead, we might see optimal mitochondria: artificially created biological machines that do the same job, but designed to remove the issues that cause harm and aging in the natural version.

The ability to insert new mitochondria is a viable approach for genetic diseases, where the patient's lineage is damaged. The new fully functional mitochondria will dilute the effects of the established mitochondria, and may largely replace them with time. Thinking on this points out the major issue with wholesale mitochondrial replacement, however: it's not the case that functional mitochondria will necessarily out-compete non-functional mitochondria within a cell over the long haul. Consider that the situation becomes something like competition between bacterial strains in an enclosed environment: whichever strain has the advantage will eventually win out. This picture is complicated by the fact that mitochondria swap components among themselves, but still seems to be a useful model when thinking about results.

For the genetic disease sufferers, it should be comforting to see that the researchers demonstrated repair of cells with broken mitochondria by inserting working mitochondria. For aging, however, the picture is less certain. After all, the problems caused by damaged mitochondria in aging occur because these damaged cellular components have an advantage to survival - they are damaged in a way that evades the surveillance mechanisms designed to weed out broken, harmful mitochondria. So it isn't clear that throwing in a bunch of working mitochondria will help all that much; one might imagine a short-lived benefit, but then you're right back to where you were before.

Which is not to say that people shouldn't try this. I say run up some old flies or nematode worms and infuse them with fresh new mitochondria, see what happens. A study in nematodes in particular should proceed fairly straightforwardly from being able to do this in cell cultures.