Aging entails a plethora of changes at multiple levels ? affecting molecules, cells, tissues, organs and integrated organisms -- which culminate in a concerted decline in overall health and ultimately death. Aging is also considered a significant risk factor for many conditions and diseases, such as cardiovascular diseases (CVD), atherosclerosis, sarcopenia, osteoporosis, renal failure and neurodegenerative diseases. Whereas significant progress has been made in understanding several of the cell intrinsic molecular pathways and cellular responses that drive aging, it is very challenging to assess the progression of aging and aging-related conditions, and the field is clearly lacking robust biomarkers for aging. We propose to use our pioneering work in cellular senescence in combination with state-of-the-art proteomics technologies to develop robust senescence-related biomarkers of aging. These novel aging biomarkers are expected to become critical research tools both for transforming the way how to look at human aging and for predicting health outcomes based on biological age and not chronological age (years of age). In parallel, we will refine these biomarkers also for animal studies to gain greater insights into mechanisms of Biology of Aging.
There is an urgent need for Biomarkers of Aging to predict and monitor age-related conditions and complex phenotypes of aging. We propose to develop robust biomarkers and high-throughput proteomics assays for proteins that are regulated and secreted during cellular senescence. After thorough validation of these candidates as biomarkers of aging they will be quantitatively measured in plasma and plasma exosomes from human aging cohorts, and subsequently correlated to aging and specific health outcomes.
