title: Employing biomarkers of healthy ageing for leveraging genetic studies into human longevity.
abstract: Genetic studies have thus far identified a limited number of loci associated with human longevity by applying age at death or survival up to advanced ages as phenotype. As an alternative approach, one could first try to identify biomarkers of healthy ageing and the genetic variants associated with these traits and subsequently determine the association of these variants with human longevity. In the present study, we used this approach by testing whether the 35 baseline serum parameters measured in the Leiden Longevity Study (LLS) meet the proposed criteria for a biomarker of healthy ageing. The LLS consists of 421 families with long-lived siblings of European descent, who were recruited together with their offspring and the spouses of the offspring (controls). To test the four criteria for a biomarker of healthy ageing in the LLS, we determined the association of the serum parameters with chronological age, familial longevity, general practitioner-reported general health, and mortality. Out of the 35 serum parameters, we identified glucose, insulin, and triglycerides as biomarkers of healthy ageing, meeting all four criteria in the LLS. We subsequently showed that the genetic variants previously associated with these parameters are significantly enriched in the largest genome-wide association study for human longevity. In conclusion, we showed that biomarkers of healthy ageing can be used to leverage genetic studies into human longevity. We identified several genetic variants influencing the variation in glucose, insulin and triglycerides that contribute to human longevity.
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; Max Planck Institute for Biology of Ageing, P.O. Box 41 06 23, 50866 Cologne, Germany. Electronic address: Joris.Deelen@age.mpg.de.
authors.forename: Joris
authors.initials: J
authors.lastname: Deelen
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; Delft Bioinformatics Lab, Delft University of Technology, P.O. Box 5031, 2600 GA Delft, The Netherlands. Electronic address: E.B.van_den_Akker@lumc.nl.
authors.forename: Erik B
authors.initials: EB
authors.lastname: van den Akker
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: S.Trompet@lumc.nl.
authors.forename: Stella
authors.initials: S
authors.lastname: Trompet
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: D.van_Heemst@lumc.nl.
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: S.P.Mooijaart@lumc.nl.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: P.Slagboom@lumc.nl.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Electronic address: M.Beekman@lumc.nl.
authors.forename: Marian
authors.initials: M
authors.lastname: Beekman
mesh_terms: D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007328:Insulin / Q000097:blood; D016014:Linear Models; D008136:Longevity / Q000235:genetics*; D008297:Male; D009426:Netherlands; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D014280:Triglycerides
keywords: Biomarkers; Genetics; Healthy ageing; Human longevity