Cellular senescence is a process where healthy cells become non-replicative and begin inducing inflammation in the body. Studies have shown that senescence increases with age in all of us and across all tissues, and that it plays a role in age-related disease. One promising technique for identifying each individual’s senescence burden is through measurement of senescence-associated proteins (SAP) in circulating plasma. Plasma senescence has been associated with age and age-related disease, and interestingly, in recent years a group of natural compounds have been identified – known as senotherapeutics – that can selectively kill senescent cells while leaving healthy cells mostly unscathed. These compounds have demonstrated an ability to lower plasma senescence burden and to partially alleviate some inflammatory diseases. These compounds, such as Quercetin from apples and Fisetin from Strawberries, mostly come from fruits and vegetables, so the old saying “An apple a day keeps the doctor away” seems to be true.
One challenge in understanding senescence is that SAP are numerous and different by cell type. Identifying a small panel of clinically relevant SAP will allow us to potentially measure each individual’s senescence burden in a non-invasive way, thus identifying candidates for senotherapeutics, and could allow us to assess the efficacy of novel senotherapeutics that arise in the future. In this study I work with SAP that have been identified in many tissues, and I am able to track levels of these proteins in the plasma in a large cohort from the UK Biobank. In this way I can find associations between senescence proteins in the plasma and age-related decline and disease, with the ultimate goal of identifying clinically relevant SAP. Because the pool of SAP is large, I rely on established machine learning techniques to help me wade through the SAP in order to identify among them those that appear to have a deleterious impact on human health.
This study, with a projected duration of less than 36 months, aims to understand the role that senescence plays in the aging process, and to identify biomarkers of senescence, which could enable the development of better ways of combating senescence-related disease in the future.
