MitoSENS Mitochondrial Repair Project

Engineering backup copies of mitochondrial genes to place in the nucleus of the cell, aiming to prevent age-related damage and restore lost mitochondrial function.

By Dr. Matthew "Oki" O'Connor

Funding Successful. This project reached its goal before October 26, 2015.

  • $46,128

    Pledged of $30,000 Goal

  • 400

    Backers

  • campaign complete

This campaign will only be funded if at least $30,000.00 is pledged by October 26, 2015.

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A big thank you to everyone for helping us hit our goal so quickly! Please check out the campaign updates tab to learn about our stretch goals for hitting $45,000 and $60,000.
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Each cell in the body is dependent on the efficient generation of cellular energy by mitochondria to stay alive. Critical to this process are genes encoded within the mitochondrial genome. Over time however, mutations in these genes occur as a result of constant exposure to reactive oxygen species produced by oxidative phosphorylation, the mitochondrial energy generation process. Unlike genes within the nucleus, mitochondria lack an efficient system to repair damaged DNA. This leads to accumulated mutations, resulting in mitochondrial defects and an increase in oxidative stress throughout the body. Closely correlated with this is the observation that organisms which age more slowly also consistently display lower rates of mitochondrial free radical damage. Thus, reversing and/or preventing damage to mitochondrial DNA may be a key factor in slowing the aging process.

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 protein coding 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.

Edward James Olmos describes the SENS Mitochondrial Repair Plan

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 (see figure below). 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 a significantly higher efficiency of import to mitochondria than any previously published research.

Visualization of engineered ATP8 expressed in mutant cellsSENS-data-slide

Successfully completing this project will mean that we have developed a groundbreaking method that will provide us with the capability to safeguard the mitochondrial genome by creating a backup copy in the nuclear genome. The overall goal will be to test this improved targeting technology so that it can be optimally refined for use in rescuing mutated mitochondrial DNA, and thus prevent and cure what may be one of the major causes of cellular aging.

In our current research, we are using cells derived from a patient suffering from a rare mitochondrial disease, that are null for the mitochondrial ATP8 gene (i.e., the ATP8 protein is completely absent). We have inserted our improved versions of the ATP8 gene, equipped with our specialized mitochondrial tagging system, into the nuclear genome. Inserting it into the nuclear genome helps to protect the gene from oxidative damage, while our tagging system will help guide the functional protein into the mitochondria where it is needed.

We need your support at this critical juncture of the MitoSENS project. The MitoSENS team has already demonstrated the rescue of cells containing mitochondrial mutations, and has recently generated highly promising preliminary data showing the rescue of the complete loss of a mitochondrial gene. Our next steps will focus on improving the effectiveness of the targeting system, so that we can repeat our success with one mitochondrial gene to all thirteen. We will then transition this work into animal models of mitochondrial dysfunction. This would be a crucial step in what may be the development of an eventual cure for aging and aging related diseases.

We have a talented team of highly trained mitochondrial biologists working on MitoSENS. Right now the rate-limiting factor is the cost of the expensive reagents that we use for these experiments. Increasing our funding with this campaign will allow us to double the pace of our research and bring results to the public that much faster. We have made preliminary progress on rescuing function with a second gene, ATP6, and your support will help us perfect our targeting of both ATP8 and ATP6. This requires more cells, more viruses, and many new synthetic gene sequences. Specifically, we will spend your generous donations on cell culture reagents, oxygen consumption measurements, virus production, quantitative reverse transcription PCR, DNA synthesis services, and publication of our results in a peer-reviewed journal.

Your support will help take us there.

Thank You.

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Great Success Thus Far!

Posted on 05-18-2016 by Matthew O'Connor

Hi Everyone, it’s been an amazing few months. In short, we have been tremendously successful in our efforts to rescue a mutation in the mitochondrial genome!

PrintEssentially we’ve shown that we can relocate both ATP6 and ATP8 to the nucleus and target the proteins to the mitochondria. We can show that the proteins incorporate into the correct protein complex (the ATPase) and that they improve function resulting in more ATP production. Finally, we show that the rescued cells can survive and grow under conditions which require mitochondrial energy production while the mutant cells all die.

We have finished writing up our results and submitted them for review and publication. It may take a while for our results to be published (the peer review process can be lengthy) but as soon as it is I’ll post an update here so you can see the full paper.

We have also started the project that you helped us get to our stretch goal on. We have made all the combinations of MTS with ATP6 that we proposed and are now working on testing them. I’ll let you know when we know more.

Thank you so much for your support!

Oki


Updates

Posted on 10-19-2015 by Matthew O'Connor

MitoSENS_Oki_Thumbs_up_inside_CC

Hi everyone, thanks so much for your support in reaching our initial goal! I’m proud to announce that we have just received a donation from a local company in the form of a large quantity of free DNA primers. We used the donation to design a huge set of primers that we can use to make dozens more mitochondrial targeting sequences (MTSes) to test for their ability to target proteins to the mitochondria. So instead of the 3 that we’ve tested so far we could test many different ones that we suspect might be good candidates as stretch goals for this campaign.

If we reach a total of $45,000 we can test all of these MTSes on ATP6 and see if we can bring it up to full activity.

If we reach a total of $60,000 we can also test all of these targeting signals on a 3rd gene, Cytochrome B, which has long been a challenging gene for us and others in the field to make functional. If we can get this gene working, we should be able to make any gene in the system work.

In addition, we are excited to announce matching funds! Several of you have asked for this. For every dollar that you donate to the Mitochondrial Repair Project another dollar will go directly into the SENS Research Foundation general fund to support all the great research we do at SRF. Thanks to Reason at fightaging.org for helping to organize this fund to match your donations!


32 Comments

  1. Reuben Tracey Reuben Tracey

    What a great Site, and its great to see SENS the first project, here, of course I had to back it.
    This is really important project and I really hope they meet there goal.

      • John

        That analysis showed a link between using PGP to limit mitochondrial swelling in mice tissues, which is rather interesting as a topic but unhelpful long term. In addition to disputing the relevance of your source trial (which doesn’t appear to offer a duration or suggestion that the tests increase healthy lifespan of the mice in question), I’d like to point out that protection is less beneficial in the long term, because you cannot stop damage from occurring completely no matter how well you defend an organelle, and that damage will accumulate over time. The only option is to repair or replace the damaged component which is why this sort of project is rather important.

      • Antonio

        (1) Ginseng extracts aren’t natural.
        (2) Natural products aren’t better than artificial ones.
        (3) Ginseng doesn’t protect against mitochondrial DNA damage.
        (4) This research has nothing to do with hipoxia.

  2. Giancarlo Aguirre

    WoW, now I can feel I’m helping a good cause, good, if there is another promising project for increasing life expentancy and /or reverse aging, let us know, I’ll be glad to back it up :).

  3. Gennady Stolyarov II Gennady Stolyarov II

    Best wishes on the success of this important research project – another step forward in the noble and urgently necessary war against senescence and death.

  4. Prayag Patil

    Have never seen a worthier project, clear concise goals with obvious reward in terms of improving our ability to reengineer ourselves.

  5. Brett Bellmore

    A worthwhile project to engineer a future humanity, and I’ll see if I can’t contribute, but I’d also like to see something with more theraputic potential for existing old geezers such as myself. Mitochondria *evolve* within the cell dependent on a host of circumstances, and are quite capable of remaining functional indefinately if subject to the right evolutionary ‘incentives’.

    We need to engineer circumstances such that the working mitochondria will outcompete the disfunctional ones.

  6. Jim

    I mentioned this over at the http://www.fightaging.org website – how about rather than just being a kickstarter style website lifespan.io could provide fundraiser tools? Rather than just chuck in whatever dollars I could afford and then send the page for this project to my friends, hoping they donate too, I could run a half marathon or something to raise money from my friends, much like people do with cancer etc?

    There are sites out there like http://www.justgiving.com that facilitate this already, but they take a fairly hefty approach to the fees they charge. How difficult would it be to add such facilities to lifespan.io?

    Not only could this help raise more money, it is also a promotional tool.

      • Jim

        Keith, it seems like you already have most of the infrastructure ready to go. If you could just create a private page that only people with a link could view (or just not a page with hyperlinks from the rest of the website) . I can’t afford to give much to the Mitosens campaign personally, but I might be able to raise 250-500 dollars from friends & relatives for an activity.

  7. Aaron

    Can anyone contact me to give a bit more info about the tshirt that comes with the $50 donation? I have unique fit needs so I’d like to get some details to make sure it’ll work. Thanks much. Go longevity! ;-)

  8. Victor

    What an amazing idea! I have not contributed yet, but I will. One thing that I want to suggest is different rewards: I personally don’t care about T-shirts and all that merchandise, but I would love to receive an in-depth explanation of the problem with mitochondrial mutations and the suggested solution. This would be a great perk that would help me deepen my understanding and be more involved – as I really wish I could be (I don’t have much money to support but I could contribute my time and would love to know how to do it).

    • Keith Comito Keith Comito

      Hi Victor; some of the mid-level rewards like the 30 minute video call with the team would be perfect for this sort of thing. Obviously these rewards are at higher contribution levels, but they do require the researchers to set aside time, etc.

  9. Matthew O'Connor Matthew O'Connor

    Hi everyone, in addition to all the wonderful financial support we’ve received during this campaign we’ve also had a number of inquiries about volunteering. Volunteers and interns are a huge part of SRF. If you’d like to inquire about volunteer opportunities please fill out an application so we can try to find the best way for you to help. http://www.sens.org/outreach/take-action/volunteer Please be patient as we’ve seen quite an uptick in applications this past month.

    -Oki

  10. John

    Guys, I really don’t want to register on another site. Can you work out a way for me to just plop down 10 bucks via paypal or something and do nothing else?

    Maybe I’m the only one this is bothering; if that’s the case then forget it, obviously, I’ll suck it up and do it :)

    • Keith Comito Keith Comito

      At the moment the limits paypal wanted to impose on the crowdfunding transactions made it essentially impossible to use for any real scenario. You can use paypal to donate directly to LEAF if you like, however, via the donate link in the header.

  11. Eric Schulke

    Thank life for every one of you health extending donators. You are leaders, pure and simple. That’s no overstatement. Small donations, big donations, they all lead the way for more in a big way, and in more ways than one.

  12. Antonio

    Less than $900 to go :) Since there are still 28 days left, will the project scope be extended and a new funding goal set?

  13. Giancarlo Aguirre

    You have reached the goal, now I’m sure that you would be able to do more if you pass the number, you should put another project, and I’m surprise other investigations and projects about aging hasn’t appeared in the site, is it taking so long to approve? or there is no projects jet to be fund?

    • Eric Schulke

      There are more projects lined up, but we’re waiting until we have a bit more time on our hands to jump in again. It takes a ton of effort to raise this kind of money in our relatively small, but growing communities. If you or anybody wants to join in on helping to promote the next ones then let us know.

  14. John G

    Love the research potential, I will be adding my $100 worth – good luck.
    Question 1: Any way for me to decline material “goodies” ? I would love to have a low-cost ecopy of the book and would like to see all more go towards research (dont need a tshirt, bag, etc. as cool as they are :-) ).
    Question 2: Does this count towards the 2015 Challenge Grant shown on sens.org ? Or am I better donating directly through sens.org to help take advantage of that?

    • Keith Comito Keith Comito

      Hi John, here are the answers to your questions:
      1. You could definitely email SENS and make this request. We’ll pass the info along as well.
      2. All donations made after Oct 1 on Lifespan.io will also count towards the SENS matching fundraiser.

    • Keith Comito Keith Comito

      Hi Nadav, this would likely depend on the item and how SENS will be shipping. Feel free to contact them for specifics. Otherwise they would contact you after the campaign ends to figure this out. Thanks.

  15. Rick Davis

    Where can we go to follow the progress of this research? A note every week or every other week would foster a sense of participation that might boost future donations. It might be as simple as “ordered supplies” or “started x experiment”.

    • Keith Comito Keith Comito

      Hi Rick, there is an updates tab in the campaign where Dr. O’Connor can provide updates as milestones are hit. I will be in contact with him about this. Additionally you may be contacted by SENS via email, newsletter, etc.

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  • Grant Simmons
    $25.00
  • Rodney Skilton
    $20.00
  • michael brown
    $20.00
  • Carl White
    $50.00
  • Darrin
    $20.00
  • douglas marsh marsh
    $10.00
  • Matthew O'Connor
    $20.00
  • Mary Beth M
    $20.00
  • Daniel Scott
    $20.00
  • Edward Lemon
    $50.00
  • Jeff Pizanti
    $20.00
  • Anonymous
    $20.00
  • David Chambers
    $100.00
  • Grego
    $20.00
  • Lee Wegenast
    $20.00
  • Norbert Harjadi
    $20.00
  • Brandyn Webb
    $10.00
  • Terry Cole
    $20.00
  • Louis Burke
    $25.00
  • Donald Alligood
    $20.00
  • Mark Penner
    $20.00
  • Nick Shapiro
    $20.00
  • Jet Lee
    $50.00
  • Leroy Arellano
    $100.00
  • Jonathan West
    $10.00
  • Eric Schulke
    $50.00
  • David Stephens
    $150.00
  • Charles Esterbrook
    $100.00
  • Maria Konovalenko
    $100.00
  • Francisco Javier Quero Lombardero
    $10.00
  • Alain Domissy
    $50.00
  • Michael Bergerson
    $250.00
  • Nathan Murfey
    $25.00
  • Dean Smart
    $25.00
  • Lars Claussen
    $125.00
  • Sebastian Hagen
    $499.00
  • Veronica Gaglione
    $50.00
  • Curry Taylor
    $250.00
  • Arsen Zahray
    $150.00
  • Cryonica Lamm
    $50.00
  • Benjamin Van Eerden
    $30.00
  • Raymond Gough
    $10.00
  • Dustin D. Trammell
    $150.00
  • Brandon Reinhart
    $5,000.00
  • Mike Williams
    $50.00
  • Cameron Bloomer
    $70.00
  • Rick Davis
    $50.00
  • Darrell Weaver
    $25.00
  • Bence Kodaj
    $70.00
  • Florent Berthet
    $10.00
  • Audrey Quach
    $50.00
  • Jeremy Schlatter
    $200.00
  • Aaron Dallin
    $50.00
  • Thomas Murtagh
    $10.00
  • Sagan Bolliger
    $25.00
  • Nathan Lefler
    $25.00
  • Daniel Lemire
    $10.00
  • Dean Pomerleau
    $10.00
  • Prayag Patil
    $1,000.00
  • James Grugan
    $10.00
  • Kurren Nischal
    $50.00
  • Ryan Berkani
    $14.00
  • Jarrad Hope
    $500.00
  • Anders Grönnevik
    $10.00
  • Benjamin Short
    $150.00
  • Tom Sanders
    $50.00
  • abraham jaleel
    $25.00
  • Gennady Stolyarov
    $100.00
  • André Heinonen
    $25.00
  • Nell Watson
    $10.00
  • Paul Spiegel
    $50.00
  • Zoltan Istavn
    $10.00
  • Robert McBrayer
    $50.00
  • Morten Weinreich
    $10.00
  • Gianluca Tabbita Bonifazi
    $25.00
  • Michael Marye
    $150.00
  • Walter Crompton
    $25.00
  • Giancarlo Aguirre
    $10.00
  • Gianluca Tabbita Bonifazi
    $10.00
  • Marcel
    $25.00
  • Corbin
    $25.00
  • Horia Dumitru
    $10.00
  • William DeVore
    $50.00
  • Richard Heinz
    $10.00
  • Jay Lewis
    $50.00
  • Stephan Bardubitzki
    $100.00
  • Jan Wong
    $50.00
  • George Munteanu
    $10.00
  • Scott Niznik
    $50.00
  • Guillaume Galdrat
    $25.00
  • Rasmus Henriksen
    $50.00
  • Michael Greve
    $150.00
  • Reuben Tracey
    $25.00
  • Sam Holmes
    $70.00
  • Bruce Burke
    $250.00
  • Kevin Hink
    $25.00
  • Nico
    $250.00
  • Mykhailo Korbakov
    $100.00
  • Grant Takara
    $150.00
  • Omer Yousuf
    $10.00
  • Otto Valtakoski
    $10.00
  • Nicolai Kilian
    $11.00
  • Anat Paskin-Cherniavsky
    $70.00
  • Chris McAulay
    $10.00
  • Greg D'Agostino
    $100.00
  • Brian & Sabine Atkins
    $150.00
  • Zackerie Galhardo
    $10.00
  • oliver medvedik
    $10.00
  • Richard Fontanesi
    $150.00
  • Christer Holmberg
    $50.00
  • James joyce
    $10.00
  • Hunter Secrest
    $50.00
  • peter svensson
    $125.00
  • Jessica Sacco
    $50.00
  • Reason .
    $250.00
  • Christie Sacco
    $10.00
  • Bobby Andishmand
    $10.00
  • Matthew Sacco
    $25.00
  • Karen Comito
    $50.00

This Campaign has ended. No more pledges can be made.

  • 78 Backers

    WEBSITE THANK YOU PAGE — Your name listed on a special thank you page on our site; thanks for joining the cause! All higher donations will include this reward.

    Estimated delivery :
    Shortly after campaign completion
  • 40 Backers

    MITOMECH FOR PLAYERS OF MECHA GALAXY — A Promotional “Mito Mech” for players of the game Mecha Galaxy: www.mechagalaxy.com. Send your payment confirmation and player ID to 11527 to collect your Mito Mech, and the satisfaction of knowing you've helped a great cause.

    Estimated delivery :
    Shortly after pledge is made
  • 85 Backers

    $10 Pledge Reward + THANK YOU NOTE + SENS PEN — Personalized thank you note signed by Aubrey de Grey and a SENS Research Foundation Pen. (Shipping included from anywhere in the domestic US).

    Estimated delivery :
    2 months after campaign completes
  • 70 Backers

    $10 Pledge Reward + SENS FOUNDATION T-SHIRT — Wear your support for the cause with a stylish SENS Research Foundation T-Shirt. (Shipping included from anywhere in domestic US).

    Estimated delivery :
    2 months after campaign completes
  • 22 Backers

    $25 Pledge Reward + SENS FOUNDATION T-SHIRT — The SENS T-Shirt, Pen, and Personalized thank you note signed by Aubrey de Grey. (Shipping included from anywhere in domestic US).

    Estimated delivery :
    2 months after campaign completes
  • 28 Backers

    $25 Pledge Reward + SENS FOUNDATION TOTE BAG AND NOTEBOOK — Custom SENS Foundation Tote Bag, including SENS Notebook, Pen, and Personalized thank you note signed by Aubrey de Grey. (Shipping included from anywhere in the domestic US).

    Estimated delivery :
    2 months after campaign completes
  • 12 Backers

    $100 Pledge Reward + SENS FOUNDATION T-SHIRT — Custom SENS Foundation Tote Bag with all the items from the $100 reward level + the SENS Foundation T-Shirt. (Shipping included from anywhere in the domestic US).

    Estimated delivery :
    2 months after the campaign ends.
  • 36 Backers
    Limit of 50 — 14 remaining

    AUTOGRAPHED COPY OF "ENDING AGING" — Personalized autographed copy of Aubrey de Grey and Michael Rae's book "Ending Aging". (Shipping included from anywhere in the domestic US).

    Estimated delivery :
    3 months after the campaign ends.
  • 18 Backers
    Limit of 30 — 12 remaining

    AUTOGRAPHED COPY OF "ENDING AGING" + $125 Pledge Reward TOTE BAG — SENS Tote Bag containing all of the items from the $125 level + Personalized autographed copy of Aubrey de Grey and Michael Rae's book "Ending Aging". (Shipping included from anywhere in the domestic US).

    Estimated delivery :
    3 months after the campaign ends.
  • 3 Backers
    Limit of 10 — 7 remaining

    30 MINUTE VIDEO CALL WITH THE TEAM — 30 minute Video Call with the members of the MitoSENS team to ask questions about the progress of the program.

    Estimated delivery :
    3 months after the campaign ends.
  • 5 Backers
    All gone!

    $250 Pledge Reward + PERSONAL VIDEO AMA WITH AUBREY DE GREY — An Autographed copy of Aubrey de Grey’s book Ending Aging and your own personal 30 minute ask me anything video call with Aubrey de Grey

    Estimated delivery :
    3 months after the campaign ends.
  • Backers
    Limit of 3 — 3 remaining

    MEET THE MITOSENS TEAM — You’ll visit the SENS Research Foundation lab to observe experiments, attend a lab meeting and be treated to lunch with the team. Travel not included.

    Estimated delivery :
    Shortly after campaign completion
  • 3 Backers
    All gone!

    DINNER WITH AUBREY DE GREY AND MATTHEW O'CONNOR + SENS RESEARCH FOUNDATION TOUR — Dinner with Aubrey de Grey and Matthew O’Connor,and a Tour of the SENS Research Foundation. Travel not Included.

    Estimated delivery :
    Shortly after campaign completion
  • Backers
    Limit of 1 — 1 remaining

    DINNER WITH EDWARD JAMES OLMOS, AUBREY DE GREY, AND MATTHEW O'CONNOR — Travel is included (from anywhere in the domestic US), as well as a two-night hotel stay.

    Estimated delivery :
    Shortly after campaign completion
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