Crowdfund the Mitochondrial Repair Project at Lifespan.io

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/

Comments

Totally behind this we need to fix mtDNA long term. I will donate what I can shortly.

Posted by: Steve H at August 19th, 2015 8:11 AM

The most exciting bit of the blurb is this:

"If, through our project, we can repeat the success in targeting one mitochondrial gene to all 13, we will be confidant in transitioning this work onto animal models of mitochondrial dysfunction".

It really would be interesting to see the effects on a mouse of being immune to this class of damage.

Posted by: Jim at August 19th, 2015 10:38 AM

Excellent initiative...

Would donate but the site won't accept my "billing address" as valid... something about my zip number being invalid (I'm in Canada).

They don't seem to allow PayPal, so...

Anyone knows where I can report such a problem?

Posted by: Daniel Lemire at August 19th, 2015 12:54 PM

@Daniel Lemire: They have a PayPal form on the main site donation page, and a link to Square as well:

https://www.lifespan.io/donate/

I sent the founders an email about the issue you found on the project donation form.

Posted by: Reason at August 19th, 2015 1:49 PM

Placed a donation :)
Hopefully this project will reach the 30k.

Posted by: Nico at August 19th, 2015 4:19 PM

"confidant in transitioning"

Woah, there's some other errors too. Mostly small ones. I'm too poor to donate money effectively, but I can dispense editorial advice for free.

FIXED VERSION OF TEXT:

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 the 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 (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 the mRNA molecule to the mitochondrial surface. Our prior research indicates that our system of tagging is significantly more efficient in importing information into mitochondria than any previously published research.

Successfully completing this project will result in the development of 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 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.

We need your support at this critical juncture of the MitoSENS project. The MitoSENS team has already generated fantastic preliminary data showing that we can rescue the complete loss of one mitochondrial gene. We have taken cells that should die, and have kept them alive and growing. If, through our project, we can repeat the success in targeting one mitochondrial gene to all 13, we will be confident in transitioning this work onto 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.

Your support will help take us there.

Thank You.

(Note: I seriously can't parse "efficiency of import to mitochondria", so I altered the statement entirely.)

Posted by: Slicer at August 19th, 2015 5:07 PM

I don't have a credit card, so I can't donate.

Posted by: Antonio at August 19th, 2015 5:48 PM

I'll be donating shortly as well. Reason posted this on reddit before, and the comments have been surprisingly supportive, with the exception of this one:

"I wouldn't say it's about 'wanting to die', but rather an acceptance of what's inevitable. Why fear what will inevitably happen? Just live your life how you choose, and then embrace death when it comes. Scurrying about trying to delay the inevitable just seems wasteful.

I can understand making your final years more comfortable and productive, but trying to extend life beyond what's normally possible and beyond what our society has adapted to just seems pointless. We haven't even really adapted to the fact that people can live to be 100, after retiring at age 60-65. . .and folks want to start living to 200 or 300?"

I realize everyone isn't going to support everything, but I hate this kind of attitude. It's almost like... why work on curing any other disease because you'll just die anyway, right?. The retirement bit aggravates me too.

Posted by: Ham at August 19th, 2015 7:14 PM

@Antonio

If you use PayPal you don't need a credit card.

Posted by: Stephan at August 19th, 2015 11:28 PM

There is no possibility to use Paypal, only credit card is admited. The link that Reason posted above is only for donating to Lifespan.io itself, not to research projects.

Posted by: Antonio at August 20th, 2015 12:15 AM

I hmessaged Keith and Oliver about adding a paypal function to projects, I will report back once i hear from them.

Posted by: Steve H at August 20th, 2015 1:03 AM

Right Keith says:

We are looking into it now; thanks. Its a bit tricky tying it into the pre-approved payments setup this style of crowdfunding uses but working on it.

Lets hope this happens soon, I will donate soon as this is fixed as I don't do credit cards. Hopefully SENS and others will launch more projects, I think this way is better than simply donating to something. I like specific projects I can choose.

Posted by: Steve H at August 20th, 2015 1:10 AM

Thanks, Steve. Let's hope it's implemented soon. Also, it's a pity that they don't send the merchandise outside the US :(

Posted by: Antonio at August 20th, 2015 2:21 AM

I have debit card but I'm not gonna expose it's number and CVV on the internet. I've donated to SENS and Maria with PayPal without any problem.

Posted by: Martin S. at August 20th, 2015 2:22 AM

These approaches are certainly useful and welcomed, however they are not "better" than simple donations. Because they cannot replace them. They're just complementary.

Posted by: Nico at August 20th, 2015 2:49 AM

Nico, I agree but they do IMO serve as more of a "call to arms", specific projects like this highlight a particular cause or aspect of the work.

For me also there are certain things sens do i support and some i do not so being able to back what i support works for me.

Posted by: Steve H at August 20th, 2015 7:16 AM

Yes Steve, the way these research projects are highlighted in "participative fundraisings" seem to have much more impact on the public.

Presented this way, a given project is more easy to grasp than if it's part of a complicated enterprise. The public, at the same time, is empowered and gets to ponder more on its own responsibility: "Should I fund this or not? Will it give me any value? What's the return on investment for me?".

I just felt the need to "defend" the traditional, general donations towards a foundation. Those should not be put aside, as they help run the organisation, allow the funding of early projects that cannot yet be curated for public support, etc.

Posted by: Nico at August 20th, 2015 12:05 PM

Hi All,

This is Keith from Lifespan.io. Thanks for the support and for helping us test the site! Here are some replies to points above:

—Typos should be fixed; let me know if you see any others.
—Canadian donations should work: Daniel did you select Canada from the country drop down box in addition to filling out your address?
—We are investing how hard it will be to add paypal support to the campaigns, as this would obviously be a good thing to do.

Thanks again, and please let me know anything else you find.

—Keith

Posted by: LifespanKeith at August 20th, 2015 1:04 PM

Hi Keith,

it would be great if we could share projects also on LinkedIn.

Posted by: Stephan at August 20th, 2015 11:44 PM

Stephan: good idea — we'll look into adding a LinkedIn button on the campaign sharing widget. You could of course just copy the URL and share it directly wherever you want as well.

Antonio: SENS actually IS able to send items internationally, it just won't be part of the price of the reward (they would contact you after the campaign to receive the extra shipping costs). This experience can definitely be smoother and we are working on it as well.

Posted by: LifespanKeith at August 21st, 2015 9:05 AM

Oh, thanks! Nice to hear that!

Posted by: Antonio at August 21st, 2015 9:06 AM

@LifespanKeith: Well, so far I have shared the project through the YouTube video. However, it would be nice to have just a button to share any upcoming project on LinkedIn.

Posted by: Stephan at August 21st, 2015 4:43 PM

BTW, maybe SENS Foundation and/or Lifespan could create their own group at LinkedIn as well. Here are business people who, hopefully, have deeper pockets to support funding.

Posted by: Stephan at August 21st, 2015 4:47 PM

"Typos should be fixed; let me know if you see any others."

Keith, "may be key factor" (should have an "a" in it), "yields in a significantly higher efficiency of import" (at the very least, that "in" doesn't belong there, or "yields" should be "results"- and laymen still don't know what "efficiency of import" means), and some minor punctuation stuff are still there.

Remember, you're trying to get money from members of the public who might not know anything about rejuvenative technologies and who may or may not be entirely willing to part with their money. If someone finds a single problem with the text, any single reason to doubt your professionalism- even if that's as small as a minor typo that makes it look like English isn't your first language (whether it is or isn't)- then that person's that much more likely to take his money and go home.

I've said it before on this site and I'll say it again: the people you need money from don't have a complete grasp of the science or terminology and may know nothing about the subject altogether, so you can't overestimate the role of fundamental marketing concepts in getting the funding you need.

Posted by: Slicer at August 22nd, 2015 12:10 PM

Thanks Slicer; those should be fixed as well.

I agree with your points, and if you (or anyone here), has a skill set they'd like to contribute in order to improve our success, please feel free to let me know. Remember that we are not a for-profit with huge investment capital; we are a small nonprofit group of individuals passionate to the cause working to get the ball rolling as fast as we can; support is welcomed!

Thanks,
Keith

Posted by: LifespanKeith at August 22nd, 2015 12:55 PM

Well, looking at your team, you seem to already have... check your email.

Posted by: Slicer at August 22nd, 2015 2:33 PM

I put a post up over at longecity about it, hopefully it will generate some more donations.

I was thinking as well about the prizes, i think a better way to do the AMA prize would have been to have a lower amount, say $50 - $100, and for that you get to submit one question that will recieve a written response from the Sens team of say between 200 - 300 words. The thing is alot of people may have a particular part of Sens that they are curious about but cant justify a $500 donation, or maybe they find video chats uncomfortable. Just a thought.

Posted by: Link at August 23rd, 2015 10:04 PM

I really hope this thing funds. If it did this approach could be used to get a bit more research for other critical path projects such as the oft mentioned Glucospane.

I see that David Sinclair's Nicotinamide project is up next. I'm taking the received wisdom on here that this approach to mitochondria won't work well. Still, it would be nice if that got funded and done to confirm the positive or negative expectations around it.

Is there anyway that a facebook post can be created that contains both the video, and donate button, and a funding tracker? It would be better to share this rather than just sharing the video.

Posted by: Jim at August 24th, 2015 6:30 AM

I'm not sure if there is a way to share things like that on Facebook. There is a way, however, to embed a campaign widget on other websites for better exposure (accessible from the "<>" symbol below the campaign video).

Posted by: LifespanKeith at August 25th, 2015 10:38 AM

It's a pleasant shock to see at least somewhat well-known, influential people appear in the donators list, especially with a few zeroes to the right.

Brandon Reinhart of Valve (Portal 2, Left 4 Dead 2) gave $5,000.

Posted by: Slicer at August 31st, 2015 12:14 PM

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.