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

Author:

Rasmussen Line Jee Hartmann12ORCID,Caspi Avshalom13,Ambler Antony4,Danese Andrea56,Elliott Maxwell1ORCID,Eugen-Olsen Jesper2,Hariri Ahmad R1,Harrington HonaLee1,Houts Renate1,Poulton Richie4,Ramrakha Sandhya4,Sugden Karen1,Williams Benjamin1,Moffitt Terrie E13

Affiliation:

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

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.

Funder

National Institute on Aging

UK Medical Research Council

Jacobs Foundation

Lundbeck Foundation

National Science Foundation Graduate Research Fellowship

New Zealand Health Research Council

New Zealand Ministry of Business, Innovation, and Employment

Publisher

Oxford University Press (OUP)

Subject

Geriatrics and Gerontology,Ageing

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