CellAge: Targeting Senescent Cells With Synthetic Biology

Designing better systems for detection and safe removal of dysfunctional “senescent” cells to improve health and treat age-related diseases.

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Senescent Cells – Taking Out the Trash for a Healthier You

Here at CellAge we believe it is a great thing to be healthy, capable and enjoying life at any age. We also believe that you deserve to have safe and effective medical treatments to make this happen, and this is why we are working hard to create breakthrough therapies that will treat one of the key reasons for age-related disease: senescent cells.

The Problem

Senescent cells are aged, damaged, and non-dividing cells that build up in the body over time, causing inflammation and contributing to diseases such as cancer, heart disease and osteoarthritis. These cells are normally disposed of by the immune system after following a self destruct program called apoptosis, but as the immune system ages it stops clearing away these cells. Imagine a city whose trash no longer gets collected; not something you want!

Thankfully exciting new research has shown the potential for a revolutionary therapy that could help postpone and treat a wide variety of age-related diseases by removing these senescent cells. Recent studies have even shown that removing senescent cells from mice dramatically increased their healthy period of life, which means the therapy helped the body to maintain healthy balance for longer.

Scientists are now considering the next crucial question, can these health benefits be translated to people? It turns out that to answer this question positively, we have to solve a key problem: we need a better way to accurately target senescent cells for removal.

The Solution

The current methods scientists use to identify and remove senescent cells have many limitations such as being too large to use in present gene therapies, being too imprecise in the range of cells affected, or simply being incomplete in cell targeting and removal. CellAge is building a new senescent cell targeting system that overcomes these limitations through the development of synthetic promoters, special DNA sequences that can regulate the activity and expression of genes:

The Details

In short, CellAge is going to develop synthetic promoters which are specific to senescent cells, as promoters that are currently being used to track senescent cells are simply not good enough to be used in therapies. The most prominently used p16 gene promoter has a number of limitations, for example. First, it is involved in cell cycle regulation, which poses a danger in targeting cells which are not diving but not senescent either, such as quiescent stem cells. Second, organism-wide administration of gene therapy might at present be too dangerous. This means senescent cells only in specific organs might need to be targeted and p16 promoter does not provide this level of specificity. Third, the p16 promoter is not active in all senescent cells. Thus, after therapies utilizing this promoter, a proportion of senescent cells would still remain. Moreover, the p16 promoter is relatively large (2.1kb), making it difficult to incorporate in present gene therapy vehicles. Lastly, to achieve the intended therapeutic effect the strength of p16 promoter to drive therapeutic effect might not be high enough.

CellAge will be constructing a synthetic promoter which has a potential to overcome all of the mentioned limitations. A number of gene therapy companies, including uniQure, AGTC and Avalanche Biotech have successfully targeted other types of cells using this technology. With your help, we will be able to use same technology to develop tools and therapies for accurate senescent cell targeting.

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We have teamed up with leading synthetic biology company, Synpromics, to create two new exciting systems for detecting and removing senescent cells. The great news is, a number of gene therapy companies, including uniQure, AGTC and Avalanche have already successfully used similar technology to target other kinds of cells; we are confident we can do the same for senescent cells.

Our primary goal with this project is the creation of SeneSENSE, a new system that can overcome the limitations of other approaches and provide researchers with an accurate way to detect senescent cells. We predict this system could also be used as a quality control step in the stem-cell therapy manufacturing process to make cell therapies safer! As we want to foster the development of senolytic therapies, we plan to give SeneSENSE to other scientists for free, to help them improve their results. We aim to have our cell detection system ready by Q4 2017 enabling researchers to benefit in the near future and helping to speed up progress.

Our secondary goal is to create SeneHEALTH, a system designed for the removal of senescent cells with a high level of accuracy. The first steps will be to treat children with progeria followed by chemotherapy patients, who could benefit from these therapies due to a higher accumulation of senescent cells.

With your help, we can develop tools and therapies for accurate senescent cell targeting and removal. Ultimately this means we could postpone and treat a wide range of age-related diseases, helping you to remain healthier as you grow older. Life should be full of joy, not pain from chronic diseases you can help us to make this a reality.

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  $20,000: Initial Goal – Candidate promoter design   Our first work project is to design candidate synthetic promoters which would be able to accurately detect senescent cells. To do that, we will analyse transcription profiles of a number of senescent cells. To cover all different senescence states, we will analyse senescent cells from different tissues and at different stage of senescence. We will use this data and proprietary bioinformatics algorithms to design genetic circuits which are specific to these cells.     cellage_goalbudget_1  
  $40,000: Stretch goal 1 – Assembly and screen   After we have designed our senescent cell specific genetic circuits, our next goal will be to perform the actual DNA assembly, along with screening for functionality. This stage will require an additional $20,000 in funding for DNA synthesis, cloning and functionally testing our promoters in different cell types through the use of flow cytometry and microscopy. At the end of this stage, we will have our lead promoters identified.     cellage_goalbudget_2  
  $80,000: Stretch goal 2 – Lead candidate optimization and validation   By taking our lead candidates through an additional round of “Design-Build-Test” cycle, we will be able to optimise the DNA sequence, add any additional specificity and exclude unwanted effects. This stage will end when we conduct a final in vitro screen which will allow us to validate specificity of our candidate promoter in different cellular contexts.     cellage_goalbudget_3  

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This project will be run by CellAge, working in close collaboration with Synpromics. The complimentary skills and experience of these two teams is the key driving force behind this project. The CellAge team has a diverse number of skills and experience on board. Our core team consists of Mantas Matjusaitis, Azuolas Ciukas and Eryk Jan Grzeszkowiak. Mantas (BSc Biomedical Science) is currently finishing his PhD in synthetic biology (University of Edinburgh) and has been involved in the SENS Education programme, resulting in a publication. Azuolas is finishing his degree in Economics and brings financial experience and business acumen to the team. He has worked in an M&A advisory boutique, Porta Finance (Rothschild’s exclusive partner in the Baltics), and KPMG’s Deal Advisory division. Last but not least, Eryk holds a BA degree in Philosophy, Politics and Economics (University of York) and is currently studying for a MSc in Human Complex Trait Genetics (University of Edinburgh). He is the author of the first Polish blog dedicated to genetic genealogy and speaks regularly on the genealogical applications of genotyping and DNA sequencing at regional and national conferences. In addition to the core team, CellAge is supported by an experienced board of advisors. Dr. Alexandra Stolzing and Dr. Juan Carlos Acosta are providing scientific guidance to the CellAge R&D program. They have both published a large number of high impact peer-reviewed articles, ranging from topics on paracrine senescence to stem cell aging. Their expertise grants CellAge access to world class scientific guidance to ensure a well-evaluated research program. Dr. Mike Capaldi, our business advisor, brings valuable insight into the business side of the project . For the last 18 years, Mike has worked in the biotech/technology sector serving as executive director on the Boards of both publically listed and private companies including Core Group plc, Oxford Asymmetry plc, Mindweavers plc, Synaptica Ltd, Scancell plc, Hunter-Fleming Ltd and CMP Therapeutics Ltd (in the latter four companies as CEO). We believe that a collaboration of many people sharing the same vision can bring a project to a whole new level and transform into a real movement. We would like to extend our deepest gratitude to our key partners who support us on this journey as well as to all the donors and supporters who are helping to make this project possible.

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In order to reach as many people as possible and to make this project even more engaging we have partnered with a number of creative technology companies. By supporting our campaign you can become a robot engineer, bioengineer or even crack DNA coding secrets to immortalize your name!

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We hope you are as excited about these rewards as we are, but in the end, the greatest reward that we hope to offer is making people live healthier lives. The possibility of this reward depends on all of us, so please consider donating and spread the word by sharing our project with your friends and family. Thank you!

New Campaign Goal Within Reach!

Posted on 02-07-2017 by Mantas Matjusaitis

CellAge Campaign Nears Finish Line | Lifespan.io

Hello friends; we have some exciting announcements! Our team has managed to secure additional funding for our work, which means that we can achieve our campaign goals even sooner!

The initial goal now stands at $20,000, with our stretch goals being reduced as well. As we have already raised over $15,000, with your generous support, this puts in excellent position to successfully complete our campaign and pursue our exciting work to target and remove dysfunctional senescent cells!

To that point; don’t forget that LongeCity is still currently running a funding match for this campaign, and all such donations count twice towards our project.

Thank you to all who have supported us thus far; together we can make it to the finish line!


LongeCity Matching $3,000 in Donations to CellAge!

Posted on 02-01-2017 by Mantas Matjusaitis

LongeCity CellAge Matching Funds | Lifespan.io

Hello friends! So far we have raised over $14,000 for the CellAge campaign, and now we have another exciting announcement: the CellAge project is now endorsed by LongeCity, one of the oldest international pro-longevity organizations! Their forum represents an exclusive education platform that has helped thousands of people learn about the endeavor to bring aging processes under medical control, remain informed about the latest breakthroughs, and develop their own strategy of health maintenance.

The LongeCity community has certified this important research project to target and remove harmful senescent cells, and is contributing $800 right away. They are also running an internal fund match: anything donated via this special page on LongeCity before February, 18 will be doubled up to $3000, and then the whole amount will be sent to support CellAge campaign on Lifespan.io. Donations made this way will still be eligible for corresponding Lifespan.io rewards, so don’t hold back!

You are very welcome to contribute, and please remember that every dollar you donate on the LongeCity page becomes two, and the project will receive a nice push to get us to our goal: control over senescent cells!


7 Comments

  1. Elena Milova

    Very interesting and promising project, good luck with the new test to identify senescent cells!

  2. Antonio

    Nice project! How does differ your approach from that of other companies like Oisin and UNITY?

    • Mantas Matjusaitis

      Hi Antonio, We are happy you like it! There is a blog post coming out to describe it in more detail so keep tuned! But in short, we are developing synthetic promoters which would be needed for senolytic gene therapy. UNITY is currently focusing on small molecules, which is potent but different approach and at this time it is hard to say which approach will be better. Oisin is also developing gene therapy, and although it is early to say, but if anything our technologies could be complementary and make an all-rounded therapy. We would like to think that more shots (approaches) we take at the same target, the higher the chances we will hit it!

        • Mantas Matjusaitis

          Hi Ibrahim,
          We are developing different type of therapies, one which will be based on gene therapy (and using synthetic promoters). Although small molecules have been the main type of medicine for many diseases, but they cannot (easily) target some of more complex diseases which have large number of pathways and factors involved. This is why we think rationally designing and engineering new medicine is the way forward.
          Mantas Matjusaitis

  3. Ekaterina Vladinova Ekaterinya Vladinakova

    Just donated to this campaign. Total this year, I’ve donated $310 to Sens RF related programs. Wish I had a higher income and I would be donating around $3000…

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    54 Backers

    THANK YOU MESSAGE ON SOCIAL MEDIA — We believe that great things can only be achieved when many people work together. Show your support for the cause to the entire world by getting yourself tagged in social "Thank You" posts which will be seen by thousands!

    Estimated delivery :
    Shortly after donation
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    108 Backers

    $1 Pledge Reward + WEBSITE WALL OF FAME — Your name listed on a dedicated page on www.CellAge.org. This page will remain active for the duration of CellAge’s existence, which we hope will be a very long time! What a great way to show that you helped create something to make people live longer and healthier lives.

    Estimated delivery :
    Shortly after donation
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    104 Backers

    $10 Pledge Reward + GET YOR NAME CODED INTO A DNA TIME CAPSULE + CELLAGE STICKERS — We will translate your name into DNA using encoding inspired by the iGEM Edinburgh team, and then store this amazing record of our early supporters in a time capsule for posterity. If that wasn’t cool enough, you will also get a pair of CellAge stickers to show off your support for longevity science!

    Estimated delivery :
    2 months after campaign completion
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    76 Backers

    $25 Pledge reward + CELLAGE DNA HOW-TO FLASH DRIVE — Receive a 16GB CellAge flash drive pre-loaded with your coded DNA sequence (see above) and a variety of tools and resources to help you explore DNA analysis and synthetic biology. This is a great way to learn more about this exciting new field which will change every aspect of our lives!

    Estimated delivery :
    2 months after campaign completion
  • 15 Backers
    All gone!

    $25 Pledge reward + ENTER RAFFLE FOR A CHANCE TO WIN iPHONE 7 WITH CELLAGE CASE! — Supporters at this level will be entered into a raffle to win a shiny new iPhone 7 (128GB) with a custom CellAge case. After the campaign ends we will randomly pick one lucky person to receive this awesome prize! *Offer void where prohibited by law. Employees, board members of LEAF or CellAge or their immediate family members are ineligible.

    Estimated delivery :
    2 months after campaign completion
  • 15 Backers
    All gone!

    $25 Pledge reward + NAME A DNA PROMOTER — You will have the opportunity to name one of the candidate promoters (subject to our approval) that we will use as part of our research to target senescent cells. There are a limited amount of promoters that we will need to screen, so hurry and name yours today. If your promoter becomes the lead candidate promoter, researchers across the world could one day be using a tool that was named by you!

    Estimated delivery :
    2 months after campaign completion
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    4 Backers

    $25 Pledge reward + PROGRAMMABLE AND UPGRADABLE ROBOT — It’s the 21st century and you still do not have your own personal robot? We know the feeling. This is why we have partnered with Robotical to offer the amazing “Marty the Robot”, a robot you can build, upgrade and control yourself! It can recognize voice commands, play football, use tools, and can be upgraded with 3D printed parts. We recommend giving it some style with the included CellAge stickers!

    Estimated delivery :
    2 months after campaign completion
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    2 Backers

    $300 Pledge reward + 30MIN VIDEO CALL WITH CELLAGE TEAM + DNA HOW-TO FLASH DRIVE — We would love to meet and speak with you about our research, future goals, and longevity science in general. This reward also combines with the programmable robot and DNA how-to flash drive, so we will have a lot of potential areas to discuss!

    Estimated delivery :
    2 months after campaign completion
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    Backers

    $50 Pledge reward + ETHNIC ORIGIN DNA TEST KIT — Do you truly know where your family originally came from? With this DNA test kit from our partner MyHeritage you find out for sure! Fingers crossed for links to Leonard Hayflick? We also include the DNA How-To flash drive so you can learn more about the processes of human DNA analysis.

    Estimated delivery :
    2 months after campaign completion
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    2 Backers
    Limit of 10 — 8 remaining

    $25 Pledge reward + JOIN 1 HOUR LIVE VIDEO CONFERENCE WITH CELLAGE, DR. AUBREY DE GREY, LIFESPAN AND OTHERS — Participate in a live-streamed video conference with the CellAge team and longevity experts across the world to discuss the latest research and developments in healthy life extension. Spaces are very limited so do not miss this opportunity!

    Estimated delivery :
    2 months after campaign completion
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    3 Backers
    Limit of 10 — 7 remaining

    $800 Pledge reward + DO-IT-YOURSELF BIOENGINEERING KIT — If you have ever wanted to get involved in biology research directly, here is an excellent opportunity to start on that path. With the help of our partner Amino Labs, we are offering this excellent DIY bioengineering kit where you can transform bacteria with DNA without the need of any other equipment. Don't forget you also get to join our live video conference so this is really a bargain!

    Estimated delivery :
    2 months after campaign completion
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    3 Backers
    Limit of 10 — 7 remaining

    $25 Pledge Reward + FORMAL ACKNOWLEDGEMENT IN PUBLISHED PAPERS / PRESENTATIONS + BRAINSTORM WITH CELLAGE TEAM — We will proudly display your name in the acknowledgments section of any peer-reviewed scientific papers and presentations resulting from the work funded by this campaign, thanking you for generously helping this important research. In addition to that, we also would like to have a video call with you to thank you personally and discuss the project in detail.

    Estimated delivery :
    2 months after campaign completion
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    1 Backer
    Limit of 5 — 4 remaining

    $2000 Pledge Reward + VISIT EDINBURGH AND DINE WITH THE CELLAGE TEAM — In addition to being acknowledged in peer-reviewed scientific papers and presentations resulting from the work funded by this campaign, you will get the chance to discuss our research personally during a 2-day stay in beautiful Edinburgh, Scotland. This includes hotel, dinner and whisky tasting with the CellAge team, and many opportunities for sightseeing and stimulating discussions! *travel not included

    Estimated delivery :
    To be agreed upon personally

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