Researchers recently demonstrated that extracellular vesicles found in urine samples could be used to assess the burden of cellular senescence in the kidneys, and that result most likely correlating well in most individuals with senescent cell numbers throughout the body. The higher the burden of senescent cells, the worse harms caused by their inflammatory secretions, contributing to the onset and progression of many age-related conditions. Here, a similar urine-focused study is undertaken, looking at a different set of molecules found in extracellular vesicles, while also showing that the approach is viable. Given the availability of first generation senolytic drugs, such as the dasatinib and quercetin combination, capable of clearing a fraction of senescent cells from old tissues, a good non-invasive assay is very much needed to show the degree to which the treatments are working.
Extracellular vesicles (EVs) possess properties related to the state of the originating cell, circulate in blood, cerebrospinal fluid, and urine, and provide paracrinehttps://en.wikipedia.org/wiki/Paracrine_signalling">paracrine and remote cell-cell communication messengers. This study investigated whether senescence-associated secretory phenotype (SASP) and immune defense factors in EVs of urine could serve as biomarkers in elderly individuals with and without a comorbidity. Urine samples from young adults and elderly individuals with and without Parkinson's disease (PD) were collected and stored. Urine EVs were separated from a drop-through solution and confirmed by verifying CD9, CD63, CD81, and syntenin expression.
The EVs and drop-through solution were subjected to measurement of SASP cytokines and defense factors. Many SASP cytokines and defense factors could be detected in urinary EVs but not urinary solutions. Elderly individuals (older than 60) had significantly higher levels of the SASP-associated factors IL-8, IP-10, GRO, and MCP-1 in EVs. In contrast, some defense factors, IL-4, MDC, and IFNα2 in EVs had significantly lower levels in elderly adults than in young adults (younger than 30). Patients with and without PD exhibited a similar SASP profile in EVs but significantly lower levels of IL-10 in the EVs from patients with PD.
This study used a simple device to separate urinary EVs from solution for comparisons of SASP and defense mediators between young adults and elders with and without PD. Results from this study indicate that aging signature is present in EVs circulating to urine and the signatures include higher inflammatory mediators and lower defense factors in urinary EVs but not solutions, suggesting a simple method to separate urinary EVs from solutions for searching aging mechanistic biomarkers may make prediction of aging and monitoring of senolytic interventions possible.