Quantification of biological age as a determinant of age-related diseases in the Rotterdam Study: a structural equation modeling approach

  • Reem WaziryEmail author
  • Luuk Gras
  • Sanaz Sedaghat
  • Henning Tiemeier
  • Gerrit J. Weverling
  • Mohsen Ghanbari
  • Jaco Klap
  • Frank de Wolf
  • Albert Hofman
  • M. Arfan Ikram
  • Jaap Goudsmit


Chronological age alone is not a sufficient measure of the true physiological state of the body. The aims of the present study were to: (1) quantify biological age based on a physiological biomarker composite model; (2) and evaluate its association with death and age-related disease onset in the setting of an elderly population. Using structural equation modeling we computed biological age for 1699 individuals recruited from the first and second waves of the Rotterdam study. The algorithm included nine physiological parameters (c-reactive protein, creatinine, albumin, total cholesterol, cytomegalovirus optical density, urea nitrogen, alkaline phosphatase, forced expiratory volume and systolic blood pressure). We assessed the association between biological age, all-cause mortality, all-cause morbidity and specific age-related diseases over a median follow-up of 11 years. Biological age, compared to chronological age or the traditional biomarkers of age-related diseases, showed a stronger association with all-cause mortality (HR 1.15 vs. 1.13 and 1.10), all-cause morbidity (HR 1.06 vs. 1.05 and 1.03), stroke (HR 1.17 vs. 1.08 and 1.04), cancer (HR 1.07 vs. 1.04 and 1.02) and diabetes mellitus (HR 1.12 vs. 1.01 and 0.98). Individuals who were biologically younger exhibited a healthier life-style as reflected in their lower BMI (P < 0.001) and lower incidence of stroke (P < 0.001), cancer (P < 0.01) and diabetes mellitus (P = 0.02). Collectively, our findings suggest that biological age based on the biomarker composite model of nine physiological parameters is a useful construct to assess individuals 65 years and older at increased risk for specific age-related diseases.


Biological age Morbidity Mortality Biologically young Elderly 



The dedication and commitment by which study participants, general practitioners, and pharmacists of the Ommoord district contribute to the Rotterdam Study are gratefully acknowledged. We thank all staff at the Rotterdam Study research center, facilitating assessment of participants throughout the years, and Frank J.A. van Rooij as data manager.


The Rotterdam Study is sponsored by the Erasmus Medical Centre and Erasmus University Rotterdam, The Netherlands Organization for Scientific Research (NWO), The Netherlands Organization for Health Research and Development (ZonMW), the Research Institute for Diseases in the Elderly (RIDE), The Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Further support was obtained from the Netherlands Consortium for Healthy Ageing. This study is supported by Janssen Prevention Centre.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Reem Waziry
    • 1
    • 2
    Email author
  • Luuk Gras
    • 3
  • Sanaz Sedaghat
    • 2
    • 4
  • Henning Tiemeier
    • 1
    • 2
    • 5
  • Gerrit J. Weverling
    • 3
  • Mohsen Ghanbari
    • 2
  • Jaco Klap
    • 3
  • Frank de Wolf
    • 3
    • 8
  • Albert Hofman
    • 1
    • 2
  • M. Arfan Ikram
    • 2
    • 6
  • Jaap Goudsmit
    • 1
    • 7
  1. 1.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  2. 2.Department of EpidemiologyErasmus Medical CenterRotterdamThe Netherlands
  3. 3.Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & JohnsonLeidenThe Netherlands
  4. 4.Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoUSA
  5. 5.Department of Social and Behavioral ScienceHarvard T.H. Chan School of Public HealthBostonUSA
  6. 6.Department of NeurologyErasmus Medical CenterRotterdamThe Netherlands
  7. 7.Amsterdam NeuroscienceAcademic Medical Center of the University of AmsterdamAmsterdamThe Netherlands
  8. 8.Department of Infectious Disease EpidemiologySchool of Public Health, Imperial CollegeLondonUK

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