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posted by cmn32480 on Monday October 05 2015, @08:45AM   Printer-friendly

Mitochondria are the organelles ("small organs") within almost all biological cells that provide energy to the cell (in the form of ATP) but they also have a number of other crucial functions and biological importance in relation to diseases and death.

The SENS Research Foundation (SRF) (Wikipedia link) co-founded by Aubrey de Grey (who also co-founded the Methuselah Foundation (Wikipedia link)) are ultimately looking for ways to defeat death, or less controversially stated "ending aging" or even less so "transform the way the world researches and treats age-related disease" and identified mitochondrial mutations as one of seven key types of cellular damage they wished to find strategies and cures against.

As part of this the SRF launched a crowdfunding campaign called the MitoSENS Mitochondrial Repair Project which has now surpassed its funding target. The aim of the project is to engineer replacements for mitochondrial genes from copies of the genome so that mitochondrial functions can restored when lost as happens during aging and mitochondrial diseases.

An excerpt from the MitoSENS funding page:

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.


Original Submission

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University of Missouri Researchers Create Embryos with Both Maternal and Paternal Mitochondrial DNA 12 comments

Scientists have recreated heteroplasmy by producing embryos with both maternal and paternal mitochondrial DNA:

A new study published in the Proceedings of the National Academy of Sciences (PNAS) from the University of Missouri has succeeded in creating embryos with "heteroplasmy," or the presence of both maternal and paternal mitochondrial DNA. This new innovation will allow scientists to study treatments for mitochondrial diseases in humans as well as the significance of mitochondrial inheritance for livestock.

When parents pass along their genes to their children, most of the DNA from the mother and father is evenly divided. However, children only receive one type of [mitochondrial DNA] from their mothers, while the fathers' mitochondrial DNA is naturally removed from the embryos. Peter Sutovsky, a professor of reproductive physiology at Mizzou and lead author Won-Hee Song, a doctoral candidate in the Mizzou College of Agriculture, Food and Natural Resources, have found a way to prevent this paternal mitochondrial DNA removal process in pig embryos, thus creating embryos with "heteroplasmy."

"As many as 4,000 children are born in the U.S. every year with some form of mitochondrial disease, which can include poor growth, loss of muscle coordination, learning disabilities and heart disease," Sutovsky said. "Some scientists believe some of these diseases may be caused by heteroplasmy, or cells possessing both maternal and paternal mitochondrial DNA. We have succeeded in creating this condition of heteroplasmy within pig embryos, which will allow scientists to further study whether paternal heteroplasmy could cause mitochondrial diseases in humans."

Autophagy and ubiquitin–proteasome system contribute to sperm mitophagy after mammalian fertilization (DOI: 10.1073/pnas.1605844113) (DX)

Previous/Related:
Project to Repair Mitochondria Funded
Three-Person Babies Could Be Possible in Two Years
U.S. Panel Gives Tentative Endorsement to Three-Person IVF
Newcastle University Study Verifies Safety of Three-Person IVF


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  • (Score: 2) by opinionated_science on Monday October 05 2015, @09:02AM

    by opinionated_science (4031) on Monday October 05 2015, @09:02AM (#245544)

    So next time you go for some vigorous exericise, thank your mitochondria because they are doing the really hard work.

    I can't see this being abused for sports at all....no really...

    • (Score: 2) by RamiK on Monday October 05 2015, @09:41AM

      by RamiK (1813) on Monday October 05 2015, @09:41AM (#245552)

      That's true to every drug. Antibiotics shortens infections thus allowing for more time to train. Maybe we should ban that as well...

      Regardless, Aubrey de Grey been presenting these ideas for some time and they withstood academic scrutiny. I don't have any idea how feasible curing old age is, but fixing known bugs in the mitochondria will definitely address some of the worse symptoms related to old age and could definitely save up money in geriatric care even in the next 20 years. That alone is worthwhile.

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    • (Score: 3, Interesting) by takyon on Monday October 05 2015, @07:06PM

      by takyon (881) <takyonNO@SPAMsoylentnews.org> on Monday October 05 2015, @07:06PM (#245770) Journal

      I can't see this being abused for sports at all....no really...

      Sports as we know them could just die due to advances like this. Aging will be slowed and reversed, skewing age brackets, artificial and synthetic organs will allow athletes to compete longer and better, gender differences will narrow, genomes will be altered, and brain implants could make movement more precise and shorten reaction times. Blade legs, chemicals, and blood doping are just the beginning.

      Society could attempt to keep all of these medical advances out of the hands of competition athletes, but at some point the advances will be so tremendous that it would become unethical to create an "athlete class". If only a few advances are permitted, bureaucrats will have to pick and choose, creating more controversy (no cannabis, cough syrup, or hair gel [science20.com] for you!) and a complicated system [usada.org].

      In the coming decades we will learn just how damaging sports can be. [wikipedia.org] The ability to repair traumatic injuries could actually breathe some life into sports and fix a health cost-benefit analysis problem [nytimes.com]. But a rejuvenated/healed player will be closer to an ubermensch than ever before.

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  • (Score: 0) by Anonymous Coward on Monday October 05 2015, @10:00AM

    by Anonymous Coward on Monday October 05 2015, @10:00AM (#245556)

    otherwise, you'll have endless growth of the human population, which is unsustainable.

    • (Score: 3, Interesting) by q.kontinuum on Monday October 05 2015, @10:12AM

      by q.kontinuum (532) on Monday October 05 2015, @10:12AM (#245559) Journal

      - Problem solved.

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      • (Score: 2) by tibman on Monday October 05 2015, @01:59PM

        by tibman (134) Subscriber Badge on Monday October 05 2015, @01:59PM (#245621)

        For sustainability you really should put age requirements on that. Might also want to ban the killing of pregnant women because i don't know if that counts as 1 or 2 and nobody here is prepared to discuss when a fetus counts as a life : P

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        • (Score: 2) by q.kontinuum on Monday October 05 2015, @02:16PM

          by q.kontinuum (532) on Monday October 05 2015, @02:16PM (#245628) Journal

          pregnant women because i don't know if that counts as 1 or 2 and nobody here is prepared to discuss when a fetus counts as a life : P

          Actually it doesn't necessarily matter in this context if the foetus counts as life. Precondition is of course that a killer also receives all the credits his victim still had.
          So in case of a pregnant woman, if the father had the credit he would get it back (it's just fair, even if the foetus is considered alive, because he never even saw the kid), if the mother had the credit the killer will get two credits anyway (either the kid is counted, or the mom still has the credit and the killer gets it as booty)

          But it's getting tasteless, and to be honest I'm a bit surprised my first reply was rated "Interesting" and only slightly relieved it at least wasn't "Insightful". I still think we need an option "Troll +1".

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  • (Score: 2) by Alfred on Monday October 05 2015, @01:24PM

    by Alfred (4006) on Monday October 05 2015, @01:24PM (#245608) Journal
    This is how the zombie apocalypse begins.
  • (Score: 2) by Jiro on Monday October 05 2015, @02:57PM

    by Jiro (3176) on Monday October 05 2015, @02:57PM (#245650)

    Replying to this seriously, these guys sound like at worst complete crackpots, at best well-meaning guys who have no idea how to actually achieve their goal. Organizations that produce, for instance, self-driving cars have all sorts of intermediate results including driving cars on closed courses, driving cars that do many things automatically but have trouble in specific situations and still need a human observer, examples of cases where the self-driving doesn't work and needs to be improved, etc. The lack of these things shows that "early stages" means "has achieved nothing meaningful".

    • (Score: 3, Informative) by takyon on Monday October 05 2015, @07:15PM

      by takyon (881) <takyonNO@SPAMsoylentnews.org> on Monday October 05 2015, @07:15PM (#245773) Journal

      Synthetic DNA has been created, mitochondrial DNA has been swapped with donor mitochondrial DNA, and mtDNA can be edited [the-scientist.com]. There are many intermediate results.

      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.

      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.

      Feel free to be skeptical, but there are "intermediate results", and they are talking about ongoing research and not about delivering a crackpot cure to backers within a year:

      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.

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      • (Score: 2) by mojo chan on Tuesday October 06 2015, @07:39AM

        by mojo chan (266) on Tuesday October 06 2015, @07:39AM (#245995)

        As someone with broken mitochondria, I wish I could sign up as a test subject for some of this stuff. Sadly I'll probably be an old man before they can fix what's wrong with me.

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        • (Score: 2) by Yog-Yogguth on Wednesday October 07 2015, @01:00PM

          by Yog-Yogguth (1862) Subscriber Badge on Wednesday October 07 2015, @01:00PM (#246425) Journal

          You're likely entirely correct, science is slow, sometimes incredibly slow, but even so I would still contact them with a few relevant details just to find out if they might be interested. Take “no” for granted and you can't lose anything by asking. I'm hazarding a guess which could be entirely wrong that a lot what they've already done has been based on cultivated cells from a tiny biopsis on someone who had already been identified as missing a mitochondrial gene (much easier to do a tiny biopsis from a human than to search for and find some human or animal with a specific missing form of ATP). I could be completely wrong.

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          • (Score: 2) by mojo chan on Wednesday October 07 2015, @03:31PM

            by mojo chan (266) on Wednesday October 07 2015, @03:31PM (#246472)

            Thanks. You know what, I will contact them.

            BTW, Truecrypt is long longer in Tails.

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            • (Score: 2) by Yog-Yogguth on Thursday October 08 2015, @09:40AM

              by Yog-Yogguth (1862) Subscriber Badge on Thursday October 08 2015, @09:40AM (#246781) Journal

              Best of luck and yes my sig had become a bit dated, tried to fix it now —thanks :)

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  • (Score: 2) by Gravis on Monday October 05 2015, @03:04PM

    by Gravis (4596) on Monday October 05 2015, @03:04PM (#245655)

    this seems like the kind of stuff that needs a basic understanding genetic engineering (from scratch) so that you can write your own genetic machinery to perform the task of organelle repair. short of this, you are just poking around a cell with a stew of chemicals.

    • (Score: 0) by Anonymous Coward on Monday October 05 2015, @05:59PM

      by Anonymous Coward on Monday October 05 2015, @05:59PM (#245738)

      Not exactly.

      What they are proposing is a off-site backup copy of 13 mitochondrial proteins. Mitochondrial targeting sequences for proteins are known and they would just have to be fused to the genes of interest. Of course the proteins may not be functional in this state and the original mutated copy may interfere with the backup.

      • (Score: 2) by HiThere on Monday October 05 2015, @06:26PM

        by HiThere (866) on Monday October 05 2015, @06:26PM (#245751) Journal

        The problem is, "How do you apply the correction where it is needed?" Perhaps it won't cause any problems if you just flood all the body with the repair medicine, but I'm not sure that's the way to bet.

        Still, if you don't look, you won't find out.

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