Abstract
Increased life expectancy is usually associated with comorbidities, such as cardio and cerebrovascular disease causing impaired functionality. A common underlying cause of these comorbidities is vascular inflammation and injury. Elevated levels of circulating microvesicles (cMV), as a product of a hemostatic and inflammatory cell activation, could be direct mapping of an imbalanced hemostasis. In this manuscript, we aimed to investigate by liquid biopsy whether successful aging can be discriminated by cMV levels and phenotype. To this purpose, we included 135 community-dwelling octogenarians in a cross-sectional study. Successful aging was defined as good functional (Barthel Index > 90 points, and Lawton index score > 7/4 points for women and men, respectively) and cognitive status (Spanish version of the Mini-Mental State Examination -MEC- > 24 points) and no need for institutionalization. Total, annexin V positive (AV+), and AV– cMV from different cell origins from the vascular compartment were phenotypically characterized and quantified from fasting plasma samples by flow cytometry. Successful aging was associated with lower plasma concentrations of total and AV+ CD141+/CD41+-CD61+, and PAC1+/AV+, CD141+/AV+, and CD36+/AV– cMV. From these phenotypes, ROC curve analyses revealed that CD141+/AV+ and CD141+/CD41+-CD61+/AV+ endothelial- and platelet-derived cMV discriminate successful and non-successful aging with an AUC (95%CI) of 0.655 (0.551, 0.758), P = 0.005, and 0.638 (0.535, 0.741), P = 0.013, respectively. In conclusion, successful aging is associated with low levels of cMV released by endothelial cells and platelets, indicating lower endothelial cell inflammation and platelet activation. Our results contribute to the understanding of the link between unsuccessful aging, cognitive decline and vascular cell inflammatory disturbances.
Highlights
Successful aging can be defined as growing old in optimum conditions (von Faber et al, 2001), considering the fact that increased life expectancy is usually associated with comorbidities, impaired functionality (Mitra et al, 2020), and diminished quality of life (Formiga et al, 2011)
As per definition, subjects with a successful aging scored higher in the Barthel and Lawton indexes, and MEC and mini-nutritional assessment (MNA) scores compared to non-successfully aged subjects
A higher proportion of subjects with successful aging were classified as functionally independent (Barthel Index > 90), able to conduct instrumental activities (Lawton Index > 7 or 4 for women and men, respectively), with high cognitive performance (MEC score > 24), and/or adequately nourished (MNA scores ≥ 24)
Summary
Successful aging can be defined as growing old in optimum conditions (von Faber et al, 2001), considering the fact that increased life expectancy is usually associated with comorbidities, impaired functionality (Mitra et al, 2020), and diminished quality of life (Formiga et al, 2011). Non-successful aging is associated with higher risk of malnutrition and falls, frailty, and with higher co-morbidity, and with cardiovascular disease (CVD) and cerebrovascular disease (Formiga et al, 2011; Beauchet et al, 2020), with vascular damage as a common underlying cause. Specific cMV phenotypes from blood and vascular cells associated with non-successful aging, may be candidate biomarkers of age-related cognitive and functional impairment. These may help in the research of prognostic biomarkers indicators of overall functional and cognitive decline in the future, and may help in the identification of subjects requiring specific strategies to prevent vascular dysfunction at the onset of cognitive and functional decline
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