(Genetic) Epidemiology of Inflammation, Age-related Pathology and Longevity

Arthur Alexander Sas

    Research output: ThesisThesis fully internal (DIV)

    423 Downloads (Pure)

    Abstract

    Ageing is associated with a low-grade elevation of inflammatory markers, attributed to the deregulation of immune and inflammatory pathways over time. This predisposes to many chronic, age-related diseases (e.g. cardiovascular disease). In other words: higher inflammatory activity means a higher disease risk (and ultimately death).

    In the present thesis, we used (classical) twin studies to estimate genetic and environmental influences on the regulation of several inflammatory markers (IL-1β, IL-6, IL-10, IgG, Fibrinogen, CRP and TNF-α). Also, the stability of these factors over time was assessed, through gene-age interaction models and longitudinal twin studies. Furthermore, the genetic and environmental overlap between neuroticism (personality trait) and inflammatory marker levels was assessed, considering their similar effects on health outcomes. Finally, the use of “simple” mathematical formulas in describing a universal “law of ageing” was discussed.

    We have shown significant genetic influences (heritabilities) on all of the observed traits throughout the thesis. The genetic factors are remarkably stable over time, indicating that differences in these phenotypes with age are largely due to changes in environmental influences (rather than different genes at different time points). A genetic overlap between neuroticism and inflammation was not observed.

    The results in the present thesis emphasize the importance of genetics in the regulation of inflammatory marker levels (and potentially the development of age-related disease). In the future, hypothetically, families at risk of higher inflammatory marker levels could be a target for prophylactic (anti-inflammatory) treatment, to reduce old-age morbidity and mortality.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Snieder, Harold, Supervisor
    • Riese, Harriette, Co-supervisor
    Award date11-Feb-2019
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-034-1377-8
    Electronic ISBNs978-94-034-1376-1
    Publication statusPublished - 2019

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