Presenting Mitochondrial Rejuvenation at a Google Tech Talk

As the clock ticks on this year's SENS rejuvenation research fundraiser - less than two weeks to go now, and plenty left in the matching fund for new donations - it is good to be reminded of the progress that the SENS Research Foundation has accomplished with the charitable funding of recent years. With that in mind, today I'll point you to a recent Google Tech Talk that provides a layperson's introduction to one of the projects that our community has funded, fixing the problem of mitochondrial damage in aging. The point of the SENS (Strategies for Engineered Negligible Senescence) research programs is to accelerate progress towards specific forms of therapy that can bring aging under medical control. To the extent that degenerative aging and age-related disease is caused at root by a few classes of molecular damage, it follows that control of aging - halting and reversing the decline - can be achieved by periodically repairing the damage. The more of it that is repaired, the better the outcome. If all of the fundamental forms of damage could be kept below the levels present in a typical 30 year old, sustained there by a package of treatments undertaken every few years, then individuals would no longer age, no longer suffer disease and frailty, and no longer suffer increased mortality with the passage of time. That, at least, is the goal. It will become clear as the research and development progresses to what degree edge cases and unforeseen issues exist.

One of the forms of damage that causes aging occurs to mitochondrial DNA. Every cell has a swarm of hundreds of mitochondria, the evolved descendants of symbiotic bacteria that over time have become fully integrated as a component part of our cells. They still divide and multiply like bacteria, and have a little of their original DNA left, completely separate from the DNA of the cell nucleus. Mitochondrial DNA encodes a few vital pieces of molecular machinery, such as portions of the electron transport chain that is used in the process of producing chemical energy store molecules to power the cell. Mitochondria are power plants, effectively, among the many other essential tasks they have adopted over the course of evolution. Unfortunately mitochondrial DNA is more vulnerable to damage and its repair mechanisms are less capable when compared to the DNA of the cell nucleus. Damage accumulates. Equally unfortunately, some forms of damage, such as large deletions that hamper the electron transport chain by denying it necessary parts, produce mitochondria that are both dysfunctional and better able to replicate and resist destruction by cellular quality control systems. A minority of cells become overtaken by these broken mitochondria as we age, and themselves become broken, generating and exporting harmful reactive molecules into our tissues. This causes enough further damage to be a significant cause of age-related disease.

The SENS Research Foundation proposes the use of gene therapy to copy these vulnerable genes into the cell nucleus, altered in order to enable the proteins produced to find their way back to the mitochondria. This produces a backup source of the proteins, and thereby eliminates the contribution of mitochondrial DNA damage to aging. This is hard work: there are thirteen genes to copy, and every one of them requires its own complicated solution to the challenge of getting the proteins back to the mitochondria. Equally, most of these genes are associated with inherited disorders, in which a patient has a damaged copy in all mitochondria. So it is possible to produce a proof of principle for a single gene and do some good at the same time. Nearly a decade ago, the SENS Research Foundation started to support work on one of these genes, NH4, that enabled a treatment for Leber's hereditary optic neuropathy (LHON). That area of research was very poorly funded at the time, and as a direct result of that SENS Research Foundation support a well-funded company is now bringing a therapy to the clinic, and looking at doing the same for other related genes. This year, the SENS Research Foundation in-house team demonstrated the same outcome for two more mitochondrial genes, ATP6 and ATP8. That work was funded by donations from people like you and I, and the researcher leading the effort recently gave a presentation in the Google Tech Talk series:

Google TechTalk: Rejuvenating the Mitochondria

"Engineering Approaches to Combating the Diseases and Disabilities of Aging: Rejuvenating the Mitochondria." This is a talk for a general audience on the work of the SENS Research Foundation to fight age related diseases with a focus on repairing the damage that accumulates as we age. The SENS Research Foundation recently published a paper on their research into repairing cells that lack two of the thirteen essential mitochondrial proteins. The SRF scientists were able to reengineer the two mitochondrial genes and move them to the nucleus of the cell, restoring the missing proteins. This work is significant for both its impact on treating age related diseases but also on childhood diseases resulting from a lack of certain mitochondrial proteins.


Great talk and very exciting stuff. Love how Blakemore etc... claimed in 2005 this was all but impossible in the near future if at all and its being done LOL

Posted by: Steve Hill at December 20th, 2016 5:21 AM

Why did it take a decade to go from NH4 to AATP6 and ATP8? I hope the rate of progress speeds up otherwise it will take ~50 years for the remaining 10 genes to be moved to the nucleus.

Also 15 years to get into the clinic! We're all going to die at this rate.

Posted by: Jim at December 20th, 2016 9:03 AM

@Jim: Low level of money coupled to it being one of the tougher challenges in the SENS portfolio.

On the 15 years to the clinic item, yes, that is slow thanks to regulation. One of the things that has to emerge in the near future is greater use of the twofold path where a company proves safety for itself and then licenses to overseas clinics at the same time as it licenses to whoever wants to run the regulatory gauntlet in the US and Europe. That way you get early availability followed by a staged progression of more data and confidence in the outcome.

Posted by: Reason at December 20th, 2016 9:21 AM
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