SRF is raising money to identify therapeutics that reduce senescent cell accumulation and extend healthspan.
SENS Research Foundation has launched the first of its experiment.com campaigns, featuring Dr Abdelhadi Rebbaa’s discovery of potential anti-senescence therapeutics.
Longevity,Technology: Aging is a risk factor for many diseases, and the accumulation of senescent cells in the body over time is a major cause of aging, with the gradual buildup of senescent cells contributing to the body’s decline in functionality. These cells produce molecules that promote inflammation and fibrosis, thereby facilitating the development and progression of chronic diseases. Examples of such diseases associated with senescence include cardiovascular diseases, neurodegeneration, diabetes, organ fibrosis, osteoarthritis and cancer. Given these connections, the identification of agents that reduce senescence burden could offer new therapeutic possibilities for addressing the aging process.
The RepleniSENS team at SENS Research Foundation is working on identifying therapeutics that will reduce senescent cell accumulation in our bodies and result, therefore, in extended healthspan. SRF is hoping to garner support for this project and thereby accelerate the creation of a novel arsenal of weapons to combat aging and prevent age-related chronic diseases.
In a campaign that runs until 15 July 2023, Dr Abdelhadi Rebbaa is hoping to raise $10,000 to discover and test novel senolytic molecules.
As we get older, the abundance of senescent cells within our bodies escalates – along with their detrimental consequences. Just employing strategies that eliminate senescent cells as they accrue may not be enough, given that these cells are perpetually generated in our bodies.
Taking that on board, Rebbaa and his team reasoned that preventing the transformation of healthy cells into senescent ones could offer a viable approach for tackling aging. To this end, they have devised a cellular model capable of identifying potential therapeutics that prevent the onset of cellular senescence. Candidate treatments will then be employed individually or in combination with senolytics to comprehensively target senescence; it is hoped this strategy will deliver superior outcomes in enhancing health during later stages of life.
Studying senescence in a dish
As a model to study senescence in a dish, Rebbaa and his team plan to use mouse embryonic fibroblasts that they will isolate from the p16 3MR mouse model. These cells express luciferase driven by the promoter of the senescence related gene p16, and this means they become luminescent when they are induced into senescence. This assay will allow the researchers to assess relatively quickly the efficacy of therapeutic candidates that inhibit senescence.
Using this cellular model, the team will screen a large library of FDA approved drugs, which contains over 1600 drugs to be tested, for the drugs’ ability to delay senescence. This will be done by forcing cells into senescence and applying the drugs; this will then allow the researchers to measure the efficacy of each drug by measuring luminescence.
The first step is likely to take up to two months, and will consist of optimizing the conditions of stress-induced luminescence and characterization of the generated senescent cells.
The library screen will follow; lasting approximately three months, the screening is expected to result in the identification of candidates that inhibit senescence.
The final part of the project is hit validation, a process taking up to one month. The team expects to identify several candidates, and depending on the results, the researchers may consider expanding the screening to a larger library of compounds.