Fight Aging!

The first project up at the newly launched longevity science crowdfunding site Lifespan.io is a mitochondrial research program to be carried out by a SENS Research Foundation scientist. This follows on from a crowdfunded initial stage in 2013 and continuing research from the past couple of years. The project is effectively an extension and expansion of the work of Gensight on allotopic expression of mitochondrial genes to cover all of the genes of interest in the mitochondria. When successful this will offer a way to bypass and eliminate the contribution of mitochondrial DNA damage to degenerative aging.

This is also a big experiment for the SENS Research Foundation: does this form of fundraising, styled after Kickstarter and Experiment, work for our community? Does it help to pull in new donors and present our goals to people who haven't yet heard of this research? Is it more or less effective than the ad-hoc methods we've used over the past decade? Further, are we at the point at which the community can run multiple distinct fundraising programs each year and still be successful in all of them? The only way to find the limits of fundraising is to keep pushing. Personally, I just pledged a few hundred dollars.

At the SENS Research Foundation, we are in the early stages of creating an innovative system to repair these mitochondrial mutations. If this project is successful we will have demonstrated, for the first time, a mechanism that can provide your cells with a modified backup copy of the entire mitochondrial genome. This genome would then reside within the protective confines of the cell's nucleus, thereby mitigating damage to the mitochondrial genome. In fact, during the long course of evolution, this gradual transfer of genetic information into the nucleus has already occurred with the majority of mitochondrial genome, leaving behind a mere 13 genes within the mitochondria. Demonstrating the effectiveness of this technology would be a major milestone in the prevention and reversal of aging in the human body.

We are also developing a unique method for guiding the products of these nuclear encoded mitochondrial genes back into the mitochondria, where they can then properly function. Over the last decade, engineering this last step has been the major bottleneck in achieving effective results. In our novel system, the mRNA from an engineered mitochondrial gene is guided back to the mitochondrial surface, where it is then translated into a protein by the organelle's co-translational import system. Once imported, it is then incorporated into the correct location within the inner mitochondrial membrane. Our precise targeting is achieved by adding a specific sequence "tag" to both ends of the mRNA. These tags then serve to guide the information containing mRNA molecule to the mitochondrial surface. Our prior research indicates that our system of tagging yields in a significantly higher efficiency of import to mitochondria than any previously published research.

In the first part of this project we will use cells that have been derived from a patient with a rare mitochondrial disease that are completely null for the mitochondrial ATP8 gene i.e. they make no ATP8 protein. We will attempt to effectively fix these cells by inserting our better engineered versions of ATP8 into the nuclear genome, rather than the mitochondrial genome, and then use our tagging system to help guide the functional protein back into the mitochondria. During the second part of this project we will then proceed to translate this technology to the remaining 12 mitochondrial genes. We have already begun recoding several of these genes in the form of cDNA constructs that can then be used to transfect our test cells.

Link: https://www.lifespan.io/campaigns/sens-mitochondrial-repair-project/