Ben says:
BSRA 2023 was a fantastic event, bringing together clinicians, scientists, policymakers and engineers, all working under the banner of ageing research. It was fantastic to meet new people working in similar areas, as well as to catch up with friends made at last year's conference. Having dinner at The Royal Society was a personal highlight, and a lovely evening was had exploring the sites of London at night. I have gotten plenty of new ideas to try, and the feedback from people interested in my poster has been invaluable.
My main takeaway would be to believe in your research and in your presentation skills! The Wednesday morning session for ECRs on presenting and communication was incredibly helpful, with lots of very helpful tips and tricks on how to be more confident in your presentations and how to pitch at the right tone for your audience. I look forward to next year's conference in Birmingham, and want to say a huge thank you to my supervisors Prof. Daniel Lambert, Prof. Graham Leggett and Dr. Caroline Evans, and to HELSI for funding the trip!
My poster, titled 'Using extracellular vesicles as a biomarker of senescence', covers some of the background behind why a novel biomarker of Senescence is required, as well as some of the techniques we are using to identify this biomarker. Senescence is a state of stable cell cycle arrest that is associated with DNA damage and ageing. The accumulation of senescent cells with age underpins many of the pathologies that are associated with ageing, such as arthritis, cancer and Alzheimer's disease. As such, the accumulation of senescent cells is being targeted as a method to combat these ageing-associated pathologies. However, to determine whether a prospective treatment is working you first need to be able to quantify the number of senescent cells present in the body before and after treatment. This is something that cannot easily be done currently.
We analysed the zeta potential of EVs isolated from senescent and healthy cells and found that there was no difference in the surface charge of these vesicles. Therefore, we determined that the zeta potential of EVs cannot be used as a biomarker of senescence.
I also covered our work on Quartz Crystal Microbalance analysis of EVs. We found that we were able to detect EV binding on the QCM sensor surface, and that there may be a difference in CD9, CD63 and CD81 expression between Senescent cell and Healthy cell-derived EVs. More work is required to prove this difference is significant, but we believe this demonstrates QCM's potential as a biomarker validation technique, as well as highlighting the potential of QCM as a research and clinical tool. This work will lead to our ultimate aim, to develop a novel nanoplasmonic sensor for the non-invasive quantification of senescence using EVs.
Research abstract:
Extracellular Vesicles as a Biomarker of Senescence
Benjamin Raven, Caroline Evans, Graham Leggett, Daniel W Lambert
An ageing population brings many challenges, with the increase in complex multimorbidities chief among them. While considerable advances have been made in the last 50 years in tackling acute illnesses, research is desperately needed to tackle the vast number of chronic, age-related conditions such as arthritis, diabetes, and Alzheimer’s disease.
Many of these ageing-associated conditions are at least partly associated with the accumulation of senescent cells, a consequence of natural ageing. These senescent cells promote, through the senescence-associated secretory phenotype (SASP), a highly inflammatory state in the surrounding tissue. The SASP also encourages surrounding healthy cells to become senescent, further promoting the build-up of senescent cells in the body.
As such, drugs are being developed to either eliminate senescent cells (senolytics) or neutralise the pro-inflammatory secretions from these senescent cells (senomorphics). However, novel senescence detection and quantification methods are required to validate whether these drugs are effective. Extracellular vesicles have been identified as a potential biomarker source for the non-invasive detection and quantification of senescence.
Extracellular vesicles are a particularly promising biomarker for the non-invasive detection of senescence due to their prevalence in saliva. This would facilitate the clinical translation of therapies targeting senescent cells, and ultimately allow the development of technology to screen for senescence, ensuring that candidates suitable for treatment are identified as soon as possible.
Here, we propose to develop novel nanoplasmonic sensors to detect extracellular vesicle-associated biomarkers of senescence in saliva. This technology could be used for drug development and for screening entire populations for the pathogenic accumulation of senescent cells in their body, facilitating the move away from reactive medicine towards beginning interventions before a patient becomes ill.