An increasing number of senescent cells in our tissues is one of the contributing root causes of aging and age-related disease. A new industry is springing up to find ways to selectively destroy these cells. CellAge is one of the more recent efforts focused on this rapidly growing field of cellular senescence. The principals aim to build better tests to assess the presence and impact of senescent cells in old tissues, based on gene promotor biotechnology. The present assays for senescent cells are showing their age; some are going on twenty years old, and they’re all fairly clunky and laborious. Clunky and laborious has been good enough for the limited amount of research work on cellular senescence that took place up until fairly recently, but is in no way a sufficient foundation for the sort of low-cost, low-effort clinical diagnostics required by the forthcoming industry of senescent cell clearance therapies. It is one thing to undergo a senescent cell therapy, and quite another to reliably and quickly understand exactly how well it performed; both removal of cells and assessment of that removal are needed for optimal progress towards widespread clinical availability.
CellAge intends to make the assays resulting from their initial development program freely available to academic groups, and has reached out to our community in search of the necessary funding. Their crowdfunding program is running at Lifespan.io, with a recently added matching fund provided by LongeCity. Meanwhile, I and a few others have been working behind the scenes to help find other sources of funding for this project, an exercise that appears to be winding to a successful close, with all the necessary paperwork to be assembled over the next couple of weeks. Along the way I think we’ve managed to make a few promising new connections for the CellAge principals, expanding the likely reach of their work. We shall see how it goes. The good news is that the combined result of these efforts and the generosity of those who donated to the crowdfunding initiative means that only a little remains to be done in order to hit the original funding target. If you have a few dollars to spare and would like to help advance research and development to treat the causes of aging, feel free to jump in here to close the last of the funding gap.
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 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.
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 dividing 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 the 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, making it difficult to incorporate in present gene therapy vehicles. Lastly, to achieve the intended therapeutic effect the strength of a 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. With your help, we will be able to use same technology to develop tools and therapies for accurate senescent cell targeting. We have teamed up with leading synthetic biology company, Synpromics, to create two new exciting systems for detecting and removing senescent cells. 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.