An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging

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  • Sayed, Nazish
  • Huang, Yingxiang
    • Other Affiliation: Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA
  • Nguyen, Khiem
    • Other Affiliation: Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA
  • Krejciova-Rajaniemi, Zuzana
    • Other Affiliation: Edifice Health Inc., San Mateo, CA, USA
  • Grawe, Anissa P.
    • Other Affiliation: Buck Artificial Intelligence Platform, the Buck Institute for Research on Aging, Novato, CA, USA
  • Gao, Tianxiang
    • College of Arts and Sciences, Department of Computer Science
  • Tibshirani, Robert
    • Other Affiliation: Department of Statistics and Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA
  • Hastie, Trevor
    • ORCID: https://orcid.org/0000-0002-0164-3142
    • Other Affiliation: Department of Statistics and Department of Biomedical Data Science, Stanford University School of Medicine, Stanford, CA, USA
  • Alpert, Ayelet
    • Other Affiliation: Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
  • Cui, Lu
  • Kuznetsova, Tatiana
    • ORCID: https://orcid.org/0000-0003-4293-4576
    • Other Affiliation: Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium
  • Rosenberg-Hasson, Yael
    • ORCID: https://orcid.org/0000-0002-3284-5732
    • Other Affiliation: Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
  • Ostan, Rita
  • Monti, Daniela
  • Lehallier, Benoit
  • Shen-Orr, Shai S.
  • Maecker, Holden T.
    • ORCID: https://orcid.org/0000-0003-0795-9946
    • Other Affiliation: Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA
  • Dekker, Cornelia L.
    • Other Affiliation: Division of Pediatric Infectious Diseases, Stanford University School of Medicine, Stanford, CA, USA
  • Wyss-Coray, Tony
  • Franceschi, Claudio
  • Jojic, Vladimir
    • Other Affiliation: Edifice Health Inc., San Mateo, CA, USA
  • Haddad, François
    • Other Affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA
  • Montoya, José G.
    • Other Affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
  • Wu, Joseph C.
    • Other Affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA
  • Davis, Mark M.
  • Furman, David
Abstract

  • While many diseases of aging have been linked to the immunological system, immune metrics capable of identifying the most at-risk individuals are lacking. From the blood immunome of 1,001 individuals aged 8–96 years, we developed a deep-learning method based on patterns of systemic age-related inflammation. The resulting inflammatory clock of aging (iAge) tracked with multimorbidity, immunosenescence, frailty and cardiovascular aging, and is also associated with exceptional longevity in centenarians. The strongest contributor to iAge was the chemokine CXCL9, which was involved in cardiac aging, adverse cardiac remodeling and poor vascular function. Furthermore, aging endothelial cells in human and mice show loss of function, cellular senescence and hallmark phenotypes of arterial stiffness, all of which are reversed by silencing CXCL9. In conclusion, we identify a key role of CXCL9 in age-related chronic inflammation and derive a metric for multimorbidity that can be utilized for the early detection of age-related clinical phenotypes.

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DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • Nature Aging
Journal volume
  • 1
Journal issue
  • 7
Page start
  • 598
Page end
  • 615
Funder
  • National Heart Lung and Blood Institute
  • National Institute of Allergy and Infectious Diseases
  • European Commission
  • National Center for Advancing Translational Sciences
  • Glenn Foundation for Medical Research
  • National Institute of Diabetes and Digestive and Kidney Diseases
  • The Ministry of Education and Science of the Russian Federation
  • National Institute on Aging
ISSN
  • 2662-8465
Publisher
  • Springer Nature

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