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.
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.
| $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. |  | |||
| $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. |  | |||
| $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. |  |
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!
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!
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!
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Very interesting and promising project, good luck with the new test to identify senescent cells!
Nice project! How does differ your approach from that of other companies like Oisin and UNITY?
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!
please can you tell more about this small molecule
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
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…
Thank you very much Ekaterinya! We really appreciate your support :)