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An Inflammatory Clock Predicts Multi-morbidity, Immunosenescence and Cardiovascular Aging in Humans
View ORCID ProfileNazish Sayed, Tianxiang Gao, Robert Tibshirani, Trevor Hastie, Lu Cui, Tatiana Kuznetsova, Yael Rosenberg-Hasson, Rita Ostan, Daniela Monti, Benoit Lehallier, View ORCID ProfileShai Shen-Orr, Holden T. Maecker, Cornelia L. Dekker, View ORCID ProfileTony Wyss-Coray, Claudio Franceschi, Vladimir Jojic, François Haddad, José G. Montoya, View ORCID ProfileJoseph C. Wu, View ORCID ProfileDavid Furman
doi: https://doi.org/10.1101/840363
Nazish Sayed
1Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
Tianxiang Gao
2Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina, 27599, USA
Robert Tibshirani
3Department of Statistics and Department of Biomedical Data Science, Stanford University, Stanford, California, 94305, USA
4Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California, 94305, USA
Trevor Hastie
3Department of Statistics and Department of Biomedical Data Science, Stanford University, Stanford, California, 94305, USA
Lu Cui
5Department of Pathology, Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
Tatiana Kuznetsova
6Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, 3000, Belgium
Yael Rosenberg-Hasson
7Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, 94305, USA
Rita Ostan
8Interdepartmental Centre L. Galvani (CIG), Alma Mater Studiorum, University of Bologna, Bologna, 40126, Italy
Daniela Monti
9Department of Experimental Clinical and Biomedical Sciences, Mario Serio, University of Florence, Florence, 50134, Italy
Benoit Lehallier
10Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, California, 94305, USA
Shai Shen-Orr
11Department of Immunology, Rapport Faculty of Medicine Technion, Israel Institute of Technology, Haifa, 32000, Israel
Holden T. Maecker
7Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, 94305, USA
Cornelia L. Dekker
12Division of Pediatric Infectious Diseases, Stanford University School of Medicine, Stanford, California, 94305, USA
13Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, 94305, USA
Tony Wyss-Coray
10Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, California, 94305, USA
14Paul F. Glenn Center for Aging Research, Stanford University School of Medicine, Stanford, California, 94305, USA
Claudio Franceschi
15IRCCS, Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, 40139, Italy
Vladimir Jojic
2Department of Computer Science, University of North Carolina, Chapel Hill, North Carolina, 27599, USA
François Haddad
1Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
José G. Montoya
16Department of Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
Joseph C. Wu
1Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
17Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA
David Furman
13Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, California, 94305, USA
18Center for Artificial Intelligence and Data Science of Aging, the Buck Institute for Research on Aging, Novato, CA 94945, USA
19Austral Institute for Applied Artificial Intelligence, Institute for Research in Translational Medicine (IIMT), Universidad Austral, CONICET, Pilar, Buenos Aires, B1630FHB, Argentina

Abstract
While many diseases of aging have been linked to the immunological system, immune metrics with which to identify the most at-risk individuals are lacking. Here, we studied the blood immunome of 1001 individuals age 8-96 and derived an inflammatory clock of aging (iAge), which tracked with multi-morbidity and immunosenescence. In centenarians, iAge was on average, 40 years lower than their corresponding chronological age. The strongest contributor to this metric was the chemokine CXCL9, which was involved in cardiac aging, affected vascular function, and down-regulated Sirtuin-3, a longevity-associated molecule. Thus, our results identify an important link between inflammatory molecules and pathways known to govern lifespan.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted November 16, 2019.
An Inflammatory Clock Predicts Multi-morbidity, Immunosenescence and Cardiovascular Aging in Humans
Nazish Sayed, Tianxiang Gao, Robert Tibshirani, Trevor Hastie, Lu Cui, Tatiana Kuznetsova, Yael Rosenberg-Hasson, Rita Ostan, Daniela Monti, Benoit Lehallier, Shai Shen-Orr, Holden T. Maecker, Cornelia L. Dekker, Tony Wyss-Coray, Claudio Franceschi, Vladimir Jojic, François Haddad, José G. Montoya, Joseph C. Wu, David Furman
bioRxiv 840363; doi: https://doi.org/10.1101/840363
An Inflammatory Clock Predicts Multi-morbidity, Immunosenescence and Cardiovascular Aging in Humans
Nazish Sayed, Tianxiang Gao, Robert Tibshirani, Trevor Hastie, Lu Cui, Tatiana Kuznetsova, Yael Rosenberg-Hasson, Rita Ostan, Daniela Monti, Benoit Lehallier, Shai Shen-Orr, Holden T. Maecker, Cornelia L. Dekker, Tony Wyss-Coray, Claudio Franceschi, Vladimir Jojic, François Haddad, José G. Montoya, Joseph C. Wu, David Furman
bioRxiv 840363; doi: https://doi.org/10.1101/840363
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