Line Jee Hartmann Rasmussen1,2, Avshalom Caspi1,3, Antony Ambler4, Andrea Danese5,6, Maxwell Elliott1, Jesper Eugen-Olsen2, Ahmad R Hariri1, HonaLee Harrington1, Renate Houts1, Richie Poulton4, Sandhya Ramrakha4, Karen Sugden1, Benjamin Williams1, Terrie E Moffitt1,3. 1. Department of Psychology and Neuroscience, Duke University, Durham, North Carolina. 2. Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. 3. Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, UK. 4. Department of Psychology, University of Otago, Dunedin, New Zealand. 5. Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, UK. 6. National and Specialist Child and Adolescent Mental Health Services Trauma, Anxiety, and Depression Clinic, South London and Maudsley National Health Service Foundation Trust, London, UK.
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.
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.
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