@article {Honge202000817, author = {Mun-Gwan Hong and Tea Dodig-Crnkovi{\'c} and Xu Chen and Kimi Drobin and Woojoo Lee and Yunzhang Wang and Fredrik Edfors and David Kotol and Cecilia Engel Thomas and Ronald Sj{\"o}berg and Jacob Odeberg and Anders Hamsten and Angela Silveira and Per Hall and Peter Nilsson and Yudi Pawitan and Mathias Uhl{\'e}n and Nancy L Pedersen and Sara H{\"a}gg and Patrik KE Magnusson and Jochen M Schwenk}, title = {Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality}, volume = {3}, number = {10}, elocation-id = {e202000817}, year = {2020}, doi = {10.26508/lsa.202000817}, publisher = {Life Science Alliance}, abstract = {Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50{\textendash}92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 {\texttimes} 10-6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95\% CI = 1.12{\textendash}1.39; P = 6.45 {\texttimes} 10-5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7{\textendash}9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.}, URL = {https://www.life-science-alliance.org/content/3/10/e202000817}, eprint = {https://www.life-science-alliance.org/content/3/10/e202000817.full.pdf}, journal = {Life Science Alliance} }