Globally, the lifespan of populations increases but the healthspan is lagging behind. Previous research showed that survival into extreme ages (longevity) clusters in families as illustrated by... Show moreGlobally, the lifespan of populations increases but the healthspan is lagging behind. Previous research showed that survival into extreme ages (longevity) clusters in families as illustrated by the increasing lifespan of study participants with each additional long-lived family member. Here we investigate whether the healthspan in such families follows a similar quantitative pattern using three-generational data from two databases, LLS (Netherlands), and SEDD (Sweden). We study healthspan in 2143 families containing index persons with 26 follow-up years and two ancestral generations, comprising 17,539 persons. Our results provide strong evidence that an increasing number of long-lived ancestors associates with up to a decade of healthspan extension. Further evidence indicates that members of long-lived families have a delayed onset of medication use, multimorbidity and, in mid-life, healthier metabolomic profiles than their partners. We conclude that both lifespan and healthspan are quantitatively linked to ancestral longevity, making family data invaluable to identify protective mechanisms of multimorbidity. Show less
Berg, N. van den; Rodriguez-Girondo, M.; Mandemakers, K.; Janssens, A.A.P.O.; Beekman, M.; Slagboom, P.E. 2020
Loci associated with longevity are likely to harbor genes coding for key players of molecular pathways involved in a lifelong decreased mortality and decreased/compressed morbidity. However,... Show moreLoci associated with longevity are likely to harbor genes coding for key players of molecular pathways involved in a lifelong decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long-lived cases with the heritable longevity trait among long-living phenocopies. To avoid phenocopies, family selection scores have been constructed, but these have not yet been adopted as state of the art in longevity research. Here, we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five-generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least two subsequent generations only when at least 20% of all relatives are long-lived. This proves the importance of family data to avoid phenocopies in genetic studies. Show less
Boer, A. de; Harteveld, A.A.; Stemkens, B.; Blankestijn, P.J.; Bos, C.; Franklin, S.L.; ... ; Leiner, T. 2020
Background: Renal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease.Purpose: To determine intrasubject test... Show moreBackground: Renal multiparametric magnetic resonance imaging (MRI) is a promising tool for diagnosis, prognosis, and treatment monitoring in kidney disease.Purpose: To determine intrasubject test-retest repeatability of renal MRI measurements.Study Type: Prospective.Population: Nineteen healthy subjects aged over 40 years.Field Strength/Sequences: T-1 and T-2 mapping, R-2* mapping or blood oxygenation level-dependent (BOLD) MRI, diffusion tensor imaging (DTI), and intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI), 2D phase contrast, arterial spin labelling (ASL), dynamic contrast enhanced (DCE) MRI, and quantitative Dixon for fat quantification at 3T.Assessment: Subjects were scanned twice with similar to 1 week between visits. Total scan time was similar to 1 hour. Postprocessing included motion correction, semiautomated segmentation of cortex and medulla, and fitting of the appropriate signal model. Statistical Test: To assess the repeatability, a Bland-Altman analysis was performed and coefficients of variation (CoVs), repeatability coefficients, and intraclass correlation coefficients were calculated.Results: CoVs for relaxometry (T-1, T-2, R-2*/BOLD) were below 6.1%, with the lowest CoVs for T-2 maps and highest for R-2*/BOLD. CoVs for all diffusion analyses were below 7.2%, except for perfusion fraction (FP), with CoVs ranging from 18-24%. The CoV for renal sinus fat volume and percentage were both around 9%. Perfusion measurements were most repeatable with ASL (cortical perfusion only) and 2D phase contrast with CoVs of 10% and 13%, respectively. DCE perfusion had a CoV of 16%, while single kidney glomerular filtration rate (GFR) had a CoV of 13%. Repeatability coefficients (RCs) ranged from 7.7-87% (lowest/highest values for medullary mean diffusivity and cortical FP, respectively) and intraclass correlation coefficients (ICCs) ranged from -0.01 to 0.98 (lowest/highest values for cortical FP and renal sinus fat volume, respectively).Data Conclusion: CoVs of most MRI measures of renal function and structure (with the exception of FP and perfusion as measured by DCE) were below 13%, which is comparable to standard clinical tests in nephrology. Show less
Berg, N. van den; Dijk, I.K. van; Mourits, R.J.; Slagboom, P.E.; Janssens, A.A.P.O.; Mandemakers, K. 2020
It remains unknown how different types of sources affect the reconstruction of life courses and families in large-scale databases increasingly common in demographic research. Here, we compare... Show moreIt remains unknown how different types of sources affect the reconstruction of life courses and families in large-scale databases increasingly common in demographic research. Here, we compare family and life-course reconstructions for 495 individuals simultaneously present in two well-known Dutch data sets: LINKS, based on the Zeeland province's full-population vital event registration data (passive registration), and the Historical Sample of the Netherlands (HSN), based on a national sample of birth certificates, with follow-up of individuals in population registers (active registration). We compare indicators of fertility, marriage, mortality, and occupational status, and conclude that reconstructions in the HSN and LINKS reflect each other well: LINKS provides more complete information on siblings and parents, whereas the HSN provides more complete life-course information. We conclude that life-course and family reconstructions based on linked passive registration of individuals constitute a reliable alternative to reconstructions based on active registration, if case selection is carefully considered. Show less
Berg, N. van den; Rodriguez-Girondo, M.; Dijk, I.K. van; Mourits, R.J.; Mandemakers, K.; Janssens, A.A.P.O.; ... ; Slagboom, P.E. 2019
