Association Between Elevated suPAR, a New Biomarker of Inflammation, and Accelerated Aging

Abstract

Background To understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline. Methods We used data from the Dunedin Study, a population-representative 1972–1973 New Zealand birth cohort (n=1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions. Results Of 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years. Conclusions Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.

Acceleration of Biological Aging and Underestimation of Subjective Age Are Risk Factors for Severe COVID-19

“…A person's physical activity, such as the number of steps taken per day, is also considered a valuable indicator of biological age [14]. There are also studies assessing the "age of the brain" [15], the emergence of biomarkers of healthy aging [16], and biomarkers in blood plasma [17][18][19][20][21][22][23]. Biological age can also be calculated using telomerase activity and telomere length [24][25][26] or the degree of DNA or histone modifications [27,28].…”

“…A person’s physical activity, such as the number of steps taken per day, is also considered a valuable indicator of biological age [ 14 ]. There are also studies assessing the “age of the brain” [ 15 ], the emergence of biomarkers of healthy aging [ 16 ], and biomarkers in blood plasma [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Eleven genomic loci affect plasma levels of chronic inflammation marker soluble urokinase-type plasminogen activator receptor

“…However, CRP and suPAR reflect different aspects of chronic inflammation despite both being used as inflammatory biomarkers 26 . In addition, unlike CRP, suPAR is a stable biomarker as circadian changes in plasma suPAR are minimal 27 – 29 , and suPAR measurements in individuals have been shown to be correlated across five and seven years 23 , 30 . We aimed to investigate whether suPAR plasma levels are under the genetic influence and if so, identify associated genetic variants that may facilitate our understanding of suPAR’s biology and its links to associated diseases.…”

Association of preoperative plasma suPAR levels with intraoperative sublingual microvascular perfusion in patients undergoing major non-cardiac surgery

“…In recent years, suPAR has been investigated as a more stable biomarker of chronic inflammation, and elevated suPAR is closely linked to accelerated biological ageing, cognitive impairment, and development of inflammation-related diseases. [33][34][35] Of note, the higher suPAR level decreases the function of the urokinase plasminogen activator receptor system in endothelial cells and may lead to microcirculatory flow abnormalities. 36 In the present study, we observed a decrease in the De Backer score, the Consensus PPV, and the Consensus PPV (small) for every 1 ng/ml increase of preoperative suPAR.…”