Rudi Gj Westendorp

..We conclude that blood monocyte telomere length is not a predictive indicator for age-related morbidity and mortality at ages over 85 years, possibly because of a high degree of telomere length instability in this group...

..The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle...

..In conclusion, we identified common haplotypes in the CFTR gene that influence survival and body composition in the population at large with no evidence for heterozygote advantage...

..In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly...

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..Nested within the Leiden 85-plus study, a population based follow-up study of the oldest old, a sample of 81 nonagenarians was recruited...

..The aim of this systematic review was to evaluate the association between subnormal vitamin B12 concentrations and anaemia in older people...

..Increasing our understanding of the aging process and applying available interventions will help to protect and preserve healthy aging...

..This observation indicates a necessity to reform the Dutch healthcare system to better meet the complex needs of older people...

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..CONCLUSION-: We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions...

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..We conclude that, in spite the effect of the ER22/23EK and N363S SNPs on metabolism, these polymorphisms together with the BclI SNP, do not affect the risks of cardiovascular disease and survival at old age...

..These findings showed that low IL-10 production capacity (i.e., a pro-inflammatory response) is associated with the metabolic syndrome and type 2 diabetes...

..Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions...

..The association of high serum concentrations of homocysteine and low folic acid with cognitive impairment in old age is likely to be a consequence of disease and not a contributory cause...

..004 and P = 0.635 respectively). We found the modified flow cytometric method measuring SA-beta-gal activity superior in discriminating between degrees of senescence in different populations of fibroblasts...

..A high innate IL-1ra to IL-1beta production capacity reflects a better ability to neutralize inflammation and may therefore protect against depressive symptoms...

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..To investigate the independent associations between medial temporal lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in the elderly...

..003) and higher fertility (P = 0.043). The results reported here provide the first evidence, based on protein production and analysis of polymorphisms, that the long pentraxin PTX3 plays a role in female fertility in humans...

..To determine whether serum calcium is associated with cognitive function in elderly individuals in the general population...

..These preliminary results suggest that memory complaints may reflect minimal brain deficits associated with impending dementia, depression or a combination of both disorders...

..The mechanism underlying this association might involve genomic instability as a result of insufficient methylation of genomic DNA...

..Especially in the oldest old, clinicians should focus not merely on common chronic diseases but particularly on general impairments as targets for diagnostic analysis and treatment to decrease walking disability...

..Low valine allele frequency resulted, however, in low power to detect statistical significance. These data suggest that an association between the Met(410)Val polymorphism and longevity in humans may exist...

..In conclusion, the i1-C/T, L1074F and C1367R polymorphisms in the WRN gene do not influence the aging-trajectories and survival in the population at large...

..In contrast to elastosis, telangiectasia may not be a good marker of the aging skin, specifically not in women...

..Handgrip strength was used as a proxy for overall muscle strength...

..08]; P < 0.001). In the oldest individual, high BP is not associated with renal function. In contrast, low DBP is associated with an accelerated decline of renal function. The clinical implications of these findings have to be studied...

..Treatment with 40 mg pravastatin daily had no beneficial effect on total CBF...

..At least part of the association between high-density lipoprotein cholesterol and cognitive function is independent of atherosclerotic disease...

..05 for both). Use of phase-contrast magnetic resonance imaging shows that hypoxia-induced cerebral vasodilatation in humans is mediated by NO...

..The added value of EEG registration in the diagnostic work-up of dementia should be further assessed in larger samples...

..029) at 3 days after irradiation. Possibly, these differences in cellular responses to stress between the TP53 codon 72 genotypes contribute to the differences in cancer incidence and longevity observed earlier for these genotypes...

..018) indicating that publication bias is at play. We conclude that, except for premature ageing syndromes, replicative capacity of fibroblasts in vitro does not mirror key characteristics of human life histories...

..There is limited insight into the attributable effect of anemia and comorbidity on functional status and mortality in old age...

..05). Pravastatin treatment in old age did not affect cognitive decline during a 3 year follow-up period. Employing statin therapy in the elderly in an attempt to prevent cognitive decline therefore seems to be futile...

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..We investigated the prognostic value of elevated erythropoietin levels on mortality among very elderly people in the general population...

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..Muscle strength measurements could be useful as part of a clinical evaluation of oldest old patients to determine who are most at risk of accelerated decline in the near future...

..To explore measures of metabolic syndrome and glucose metabolism in families with exceptional longevity...

..Furthermore, they emphasize that variation at the APOE locus has a higher impact on the risk of dementia than on the risk of cardiovascular disease in old age...

..With increasing age, these risk factors are prone to change over time. It is unclear whether dynamics of these traditional metabolic risk factors in late life associate with mortality and whether they occur in concert with each other...

..We assessed the independent predictive value of WBC count and CRP levels in relation to mortality, both vascular and nonvascular, in very old participants...

..Longevity in this study population is not compromised by the cumulative effect of this set of risk alleles for common disease...

..It is unclear whether declines in these vascular risk factors are preceded by declines in cognitive function or vice versa...

..07). Summarizing, fibroblast strains with a higher maximum replicative capacity have longer telomeres, are less prone to go into stress-induced cellular senescence, and more prone to die after stress...

..86, 95% CI: 0.50, 1.47) or cancer mortality (HR = 0.70, 95% CI: 0.30, 1.60) compared with ApoE4 carriers. These findings suggest that low cholesterol levels are not causally related to increased cancer risk...

..In conclusion, we demonstrate that genetic variation within the TLR4 gene influences cytokine production capacity, but in an endemic area does not influence the susceptibility to malaria infection or mortality...

..In conclusion, our results indicate a role for SIRT1 in cognitive functioning, but the role in life span remains to be elucidated...

..Visual impairment identifies elderly with an increased risk of cardiovascular disease...

..Within a population-based prospective follow up study of elderly people aged 85 years we show that a high innate production capacity of TNF-alpha precedes a steeper decline in muscle strength over time...

..Here, the vitellogenin family emerges as a potential key connection between lipid metabolism and the insulin/IGF-1 signalling pathway...

..To prospectively compare indicators of structural brain damage and total cerebral blood flow in patients with late-onset dementia, subjects of the same age with optimal cognitive function, and young subjects...

..These results cast further doubt on the association between in vitro growth characteristics of fibroblast cultures and the length of human lifespan...

..CONCLUSIONS: We conclude that ADL-disability is more prevalent in elderly with low income. Neither prevalence of chronic diseases nor the association with disability could explain this...

..Here, we investigate whether this observation can be confirmed for familial longevity in an outbred European population and whether it can be extended to sporadic longevity in the general population...

..In contrast, these genetic variants in the MR and GR genes do not influence cognitive functioning in old age...

..Because studies on the association of sensory impairment (both hearing and visual impairment) and cognitive functioning in elderly persons yielded conflicting results, the authors explored this association within the Leiden 85+ Study...

..Whereas the isoforms have been associated with cardiovascular disease, the relation between plasma apoE levels and cardiovascular disease is unknown...

..Despite the equivocal outcomes of randomized controlled trials, general clinical opinion favors screening and treatment of elderly individuals with subclinical thyroid disorders...

..To investigate whether a low peripheral blood lymphocyte count is associated with increased mortality risk in older persons and to determine whether this association could be ascribed to ill health...

..Thus, our results support beta-galactosidase activity as a reliable biomarker for the course of replicative senescence, if used under defined standardized conditions...

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..63; 95% CI, 0.44-0.90; p =.013), whereas for HDL cholesterol significance was lost. We conclude that high apoCI levels are associated with reduced mortality from infection, in line with experimental evidence in rodents...

..The 15-item Geriatric Depression Scale (GDS-15) is a widely used screening instrument for depressive symptoms in the elderly, but its ability to detect alterations in depressive symptoms over time has not been established...

..77; 95% CI: 0.68-0.88), while a positive association with IL-10 was found (RR = 1.22; 95% CI: 1.05-1.41). We suggest that cardiovascular mortality is a late consequence of evolutionary programming for a pro-inflammatory response...

..We studied the relationship between circulating levels of IGF1, its binding protein 3 (IGFBP3), and handgrip strength and physical performance in middle-aged- and oldest-old subjects...

..63). The results suggest that homocysteine metabolism is not likely to predict familial longevity...

..The number of cells within the colonies was modestly correlated to the growth speed of the mass cultures. We conclude that the colony formation assay does not reflect the onset of replicative senescence in human fibroblasts...

..Moreover, we describe the PHASE study, an EU-funded GWA study that will investigate the genetic variation responsible for the variation in response to pravastatin in a large randomized clinical trial...

..The basal ganglia, hippocampus, and thalamus are involved in the regulation of human feeding behavior. Recent studies have shown that obesity [body mass index (BMI; in kg/m(2)) > 30] is associated with loss of gray and white matter...

..To study the impact of a history of hypertension and current blood pressure on mortality in the oldest old...

..Research into the pathophysiology of age-associated cognitive function and decline requires a valid estimate of cognitive function. However, this estimation can be grossly influenced by a selective loss to follow-up...

..018), and higher levels of triglycerides (p =.041). Genetic variation in the gene coding for the LXRalpha (NR1H3) associates with human life span...

..440). In conclusion, in old age, except for epsilon2-allele carriers, high plasma apoE levels are associated with a higher risk of stroke, independent of APOE genotype, plasma levels of lipids, and other cardiovascular risk factors...

..The extent of atrophy showed no significant correlations. In conclusion, the MMSE scores correlate with localized depth of atrophy in well-defined periventricular structures...

..We conclude that in old age, in non-epsilon2-allele carriers, high plasma apoE levels are associated with cognitive impairments, independent of genotype, cardiovascular risk factors, and stroke...

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..To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women...

..00001). This study provides important information for the interpretation of studies reporting associations of FcgammaR alleles with disease, and underscores the apparent differences in FcgammaR heterogeneity between ethnic groups...

..Moreover, structural changes also were observed in MCI patients, indicating that widespread brain damage can be demonstrated before patients are clinically demented...

..In conclusion, although the study of model organisms has revealed potential candidate genetic mechanisms determining aging and lifespan, to what extent they explain variation in human populations is still uncertain...

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..Meta-analyses of all previous studies implied that the association in U.S. Caucasians may have its source in admixture of the U.S. control population rather than in the genetic effect of the locus on exceptional longevity...

..036) and 1.19-fold increased risk for cardiovascular mortality (P=0.052). In conclusion, this study shows that genetic variation in evolutionarily conserved Foxo1a and Foxo3a genes influences lifespan in our study population...

..The aim of the present study was to examine the effect of alpha1- and alpha2-adrenoceptor activation on nitric oxide-mediated vasodilation...

..We conclude that genes influencing amyloid-beta-induced cytokine response may provide clues to the progression of AD pathology...

..This effect was stronger for the GH1 SNP than for variation in the conserved IIS genes that were found to affect longevity in model organisms...

..The influence of seasonal changes on mood and behaviour is called seasonality. The prevalence of seasonality in elderly subjects is unknown...

..010). The IIS6 score was not associated with change in cognitive function. In addition to old age survival, genetically reduced IIS seems to be beneficial for cognitive function in women...

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..The objective of this study was to explore the relationship between home hazards and the incidence of falls in the oldest old population...

..We conclude that a malfunctioning innate immune response predicts frailty in old age and is under specific (immuno-) genetic control...