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.

Keywords: Gait speed; Immunosenescence; Inflammaging; MRI; Pace of aging.

© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.

Figures

Figure 1.

Accelerated aging and cognitive decline are associated with elevated suPAR. (A) Mean Pace of Aging (years of physiological change per chronological year), (B) mean Facial Age (z-score, mean = 0, SD = 1), and (C) mean brainAGE by suPAR quintiles at age 45 years (generalized additive models for panel A–C are shown in Supplementary eFigure 1). (D) Child-to-adult cognitive decline by suPAR quintiles. Number of participants in each suPAR quintile: Q1: n = 175 (≤2.31 ng/mL); Q2: n = 176 (2.31–2.67 ng/mL); Q3: n = 174 (2.67–3.04 ng/mL); Q4: n = 175 (3.04–3.53 ng/mL); Q5: n = 175 (>3.53 ng/mL). Error bars indicate standard error. p values for comparisons between suPAR quintiles were obtained with the Kruskal–Wallis test. BrainAGE = brain age gap estimate; suPAR = soluble urokinase plasminogen activator receptor.

Figure 2.

suPAR at age 38 is associated with physical decline from age 38 to 45. Associations (standardized β coefficients with 95% confidence intervals) of suPAR measured at age 38 with change in Facial Age, physical limitations (RAND SF36 physical functioning scale), one-legged balance, and handgrip strength from age 38 to 45. Associations were adjusted for the age 38 level of each outcome measure and sex. Change was measured as a difference score between age 45 and age 38. suPAR = soluble urokinase plasminogen activator receptor.

Figure 3.

Change in health habits is associated with change in suPAR levels. suPAR levels by smoking (A and B, n = 842) and sports/leisure-time physical activity (C and D, n = 840) categories at ages 38 and 45 years. For smoking (A and B), participants were categorized as those who never smoked (n = 424); those who were former smokers but quit before age 38 (n = 203); those who were former smokers but quit between age 38 and age 45 (n = 52); and those who were still smoking at age 45 (n = 163). For physical activity (C and D), participants were categorized as those who were physically active (ie, achieved the minimum recommended dosage of physical activity of 500 METs per week) at both ages 38 and 45 (n = 311); those who were physically active at age 38 but inactive (ie, did not achieve 500 METs per week) at age 45 (n = 221); those who were inactive at age 38 but physically active at age 45 (n = 197); and those who were physically inactive at both ages 38 and 45 (n = 111). Panels A and C show scatterplots of suPAR levels at age 38 and 45 years with black dots indicating mean suPAR. Panels B and D show mean suPAR at age 38 and 45 years with error bars indicating standard error. Note: The 2 individuals with suPAR > 10 ng/mL both had kidney disease and were undergoing dialysis. Controls for kidney disease among other conditions did not alter the findings, see Table 2. suPAR = soluble urokinase plasminogen activator receptor.