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

被引:41
作者
Rasmussen, Line Jee Hartmann [1 ,2 ]
Caspi, Avshalom [1 ,3 ]
Ambler, Antony [4 ]
Danese, Andrea [5 ,6 ]
Elliott, Maxwell [1 ]
Eugen-Olsen, Jesper [2 ]
Hariri, Ahmad R. [1 ]
Harrington, HonaLee [1 ]
Houts, Renate [1 ]
Poulton, Richie [4 ]
Ramrakha, Sandhya [4 ]
Sugden, Karen [1 ]
Williams, Benjamin [1 ]
Moffitt, Terrie E. [1 ,3 ]
机构
[1] Duke Univ, Dept Psychol & Neurosci, 2020 W Main St,Suite 201, Durham, NC 27708 USA
[2] Copenhagen Univ Hosp Amager & Hvidovre, Dept Clin Res, Hvidovre, Denmark
[3] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat Psychol & Neurosci, London, England
[4] Univ Otago, Dept Psychol, Dunedin, New Zealand
[5] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Child & Adolescent Psychiat, London, England
[6] South London & Maudsley Natl Hlth Serv Fdn Trust, Natl & Specialist Child & Adolescent Mental Hlth, London, England
来源
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES | 2021年 / 76卷 / 02期
基金
美国国家科学基金会; 英国医学研究理事会;
关键词
Gait speed; Immunosenescence; Inflammaging; MRI; Pace of aging; PLASMINOGEN-ACTIVATOR RECEPTOR; SOLUBLE UROKINASE RECEPTOR; CARDIOVASCULAR-DISEASE; NORMATIVE DATA; OLDER-ADULTS; AGE; STRENGTH; CANCER; RISK; MORTALITY;
D O I
10.1093/gerona/glaa178
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
引用
收藏
页码:318 / 327
页数:10
相关论文
共 54 条
[1]   Compendium of Physical Activities: an update of activity codes and MET intensities [J].
Ainsworth, BE ;
Haskell, WL ;
Whitt, MC ;
Irwin, ML ;
Swartz, AM ;
Strath, SJ ;
O'Brien, WL ;
Bassett, DR ;
Schmitz, KH ;
Emplaincourt, PO ;
Jacobs, DR ;
Leon, AS .
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 2000, 32 (09) :S498-S516
[2]   A clinically meaningful metric of immune age derived from high-dimensional longitudinal monitoring [J].
Alpert, Ayelet ;
Pickman, Yishai ;
Leipold, Michael ;
Rosenberg-Hasson, Yael ;
Ji, Xuhuai ;
Gaujoux, Renaud ;
Rabani, Hadas ;
Starosvetsky, Elina ;
Kveler, Ksenya ;
Schaffert, Steven ;
Furman, David ;
Caspi, Oren ;
Rosenschein, Uri ;
Khatri, Purvesh ;
Dekker, Cornelia L. ;
Maecker, Holden T. ;
Davis, Mark M. ;
Shen-Orr, Shai S. .
NATURE MEDICINE, 2019, 25 (03) :487-+
[3]   Quantification of biological aging in young adults [J].
Belsky, Daniel W. ;
Caspi, Avshalom ;
Houts, Renate ;
Cohen, Harvey J. ;
Corcoran, David L. ;
Danese, Andrea ;
Harrington, HonaLee ;
Israel, Salomon ;
Levine, Morgan E. ;
Schaefer, Jonathan D. ;
Sugden, Karen ;
Williams, Ben ;
Yashin, Anatoli I. ;
Poulton, Richie ;
Moffitt, Terrie E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (30) :E4104-E4110
[4]   Cardiorespiratory Fitness and Cognitive Function in Midlife: Neuroprotection or Neuroselection? [J].
Belsky, Daniel W. ;
Caspi, Avshalom ;
Israel, Salomon ;
Blumenthal, James A. ;
Poulton, Richie ;
Moffitt, Terrie E. .
ANNALS OF NEUROLOGY, 2015, 77 (04) :607-617
[5]   DECREASE IN TIMED BALANCE TEST-SCORES WITH AGING [J].
BOHANNON, RW ;
LARKIN, PA ;
COOK, AC ;
GEAR, J ;
SINGER, J .
PHYSICAL THERAPY, 1984, 64 (07) :1067-1070
[6]   Advances in Geroscience: Impact on Healthspan and Chronic Disease [J].
Burch, John B. ;
Augustine, Alison Deckhut ;
Frieden, Leslie A. ;
Hadley, Evan ;
Howcroft, T. Kevin ;
Johnson, Ron ;
Khalsa, Partap S. ;
Kohanski, Ronald A. ;
Li, Xiao Ling ;
Macchiarini, Francesca ;
Niederehe, George ;
Oh, Young S. ;
Pawlyk, Aaron C. ;
Rodriguez, Henry ;
Rowland, Julia H. ;
Shen, Grace L. ;
Sierra, Felipe ;
Wise, Bradley C. .
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2014, 69 :S1-S3
[7]   Upregulation of monocyte urokinase plasminogen activator receptor during human endotoxemia [J].
Dekkers, PEP ;
Ten Hove, T ;
Te Velde, AA ;
Van Deventer, SJH ;
Van der Poll, T .
INFECTION AND IMMUNITY, 2000, 68 (04) :2156-2160
[8]   The intriguing role of soluble urokinase receptor in inflammatory diseases [J].
Desmedt, S. ;
Desmedt, V. ;
Delanghe, J. R. ;
Speeckaert, R. ;
Speeckaert, M. M. .
CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES, 2017, 54 (02) :117-133
[9]   suPAR as a prognostic biomarker in sepsis [J].
Donadello, Katia ;
Scolletta, Sabino ;
Covajes, Cecilia ;
Vincent, Jean-Louis .
BMC MEDICINE, 2012, 10
[10]   Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort [J].
Elliott, Maxwell L. ;
Belsky, Daniel W. ;
Knodt, Annchen R. ;
Ireland, David ;
Melzer, Tracy R. ;
Poulton, Richie ;
Ramrakha, Sandhya ;
Caspi, Avshalom ;
Moffitt, Terrie E. ;
Hariri, Ahmad R. .
MOLECULAR PSYCHIATRY, 2021, 26 (08) :3829-3838