title: Association analysis of insulin-like growth factor-1 axis parameters with survival and functional status in nonagenarians of the Leiden Longevity Study.
abstract: Reduced insulin/insulin-like growth factor 1 (IGF-1) signaling has been associated with longevity in various model organisms. However, the role of insulin/IGF-1 signaling in human survival remains controversial. The aim of this study was to test whether circulating IGF-1 axis parameters associate with old age survival and functional status in nonagenarians from the Leiden Longevity Study. This study examined 858 Dutch nonagenarian (males≥89 years; females≥91 years) siblings from 409 families, without selection on health or demographic characteristics. Nonagenarians were divided over sex-specific strata according to their levels of IGF-1, IGF binding protein 3 and IGF-1/IGFBP3 molar ratio. We found that lower IGF-1/IGFBP3 ratios were associated with improved survival: nonagenarians in the quartile of the lowest ratio had a lower estimated hazard ratio (95% confidence interval) of 0.73 (0.59 - 0.91) compared to the quartile with the highest ratio (ptrend=0.002). Functional status was assessed by (Instrumental) Activities of Daily Living ((I)ADL) scales. Compared to those in the quartile with the highest IGF-1/IGFBP3 ratio, nonagenarians in the lowest quartile had higher scores for ADL (ptrend=0.001) and IADL (ptrend=0.003). These findings suggest that IGF-1 axis parameters are associated with increased old age survival and better functional status in nonagenarians from the Leiden Longevity Study.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands.
authors.forename: Evie
authors.initials: E
authors.lastname: van der Spoel
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands.|Netherlands Consortium of Healthy Aging (NCHA), The Netherlands.
authors.forename: Maarten P
authors.initials: MP
authors.lastname: Rozing
authors.affiliation: Department of Medical Statistics, Leiden University Medical Center, The Netherlands.
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.affiliation: Netherlands Consortium of Healthy Aging (NCHA), The Netherlands.|Section Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Netherlands Consortium of Healthy Aging (NCHA), The Netherlands.|Section Molecular Epidemiology, Leiden University Medical Center, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Beekman
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands.|Netherlands Consortium of Healthy Aging (NCHA), The Netherlands.
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands.|Netherlands Consortium of Healthy Aging (NCHA), The Netherlands.|Department of Public Health, University of Copenhagen, Denmark.
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, The Netherlands.|Netherlands Consortium of Healthy Aging (NCHA), The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008136:Longevity; D008297:Male; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I
keywords: IGF-1 axis; familial longevity; functional status; human; survival