Beenakker, Karel G.M.; Koopman, Jacob J.E.; Bodegom, David van; Kuningas, Maris; Slagboom, Pieternella E.; Meij, Johannes J.; ... ; Westendorp, Rudi G.J. 2014
Recently, it has been shown that the capacity of the innate immune system to produce cytokines relates to skeletal muscle mass and strength in older persons. The interleukin-10 (IL-10)gene... Show moreRecently, it has been shown that the capacity of the innate immune system to produce cytokines relates to skeletal muscle mass and strength in older persons. The interleukin-10 (IL-10)gene regulates the production capacities of IL-10 and tumour necrosis factor-a (TNF-a). In rural Ghana, IL-10 gene variants associated with different production capacities of IL-10 and TNF-a are enriched compared with Caucasian populations. In this setting, we explored the association between these gene variants and muscle strength. Among 554 Ghanaians aged 50 years and older, we determined 20 single nucleotide polymorphisms in the IL-10 gene, production capacities of IL-10 and TNF-a in whole blood upon stimulation with lipopolysaccharide (LPS) and handgrip strength as a proxy for skeletal muscle strength. We distinguished pro-inflammatory haplotypes associated with low IL-10 production capacity and anti-inflammatory haplotypes with high IL-10 production capacity. We found that distinct haplotypes of the IL-10 gene associated with handgrip strength. A proinflammatory haplotype with a population frequency of 43.2% was associated with higher handgrip strength (P = 0.015). An anti-inflammatory haplotype with a population frequency of 7.9% was associated with lower handgrip strength (P = 0.006). In conclusion, variants of the IL-10 gene contributing to a proinflammatory cytokine response associate with higher muscle strength, whereas those with anti-inflammatory response associate with lower muscle strength. Future research needs to elucidate whether these effects of variation in the IL-10 gene are exerted directly through its role in the repair of muscle tissue or indirectly through its role in the defence against infectious diseases Show less
Loevezijn, Ariane A. van; Cameron, Ian D; Kurrle, Susan E; Bodegom, David van 2014
Steady growth in human life expectancy has been a key feature of the last century, with projected further increases likely to have enormous impacts on societies worldwide. Despite the significance... Show moreSteady growth in human life expectancy has been a key feature of the last century, with projected further increases likely to have enormous impacts on societies worldwide. Despite the significance of these changes, our understanding of the factors shaping this trend is incomplete. During most of the historical increase, by far, the major influence was progressive decline in early and midlife death rates because of the reduction in premature deaths, caused chiefly by infection. Recent decades have seen the emergence of a new driver of increasing longevity—declining mortality among those who are old already, pointing to greater malleability in human aging than had been foreseen. There is still debate, however, as to how much of this decrease in old age mortality is caused by a better early-life environment and how much is caused by improved conditions in late life. A unique resource exists in the case of Japan, where material circumstances for the general population were consistently adverse through the early decades of the 20th century but improved rapidly after 1950. Here, we compare the Japanese birth cohorts of 1900, 1910, and 1920 and follow their period and cohort mortality trends. The results show that cohorts with similar environments early in life have very different mortality trajectories in old age. This strengthens the expectation that preventive measures in later life can deliver great benefit, while not contradicting the importance of life course approaches, to improving health and well-being. Show less
The role of individual characteristics in incidences of elder abuse has long been highest on research and policy agendas. Now, it is timely to discuss factors that go beyond victim and perpetrator.... Show moreThe role of individual characteristics in incidences of elder abuse has long been highest on research and policy agendas. Now, it is timely to discuss factors that go beyond victim and perpetrator. Environmental factors also play an important role in elder abuse. In this paper, we address the framing of elder abuse as a social and health problem. Attention is paid to the factors that influence societal context and the Healthcare system, its organization, structure, and principles Show less
Engelaer, Frouke M.; Bodegom, David van; Westendorp, Rudi G.J. 2013
For a long time, life expectancy at birth was used as the sole indicator of population health. More recently, population health is also being expressed as healthy life expectancy and it is debated... Show moreFor a long time, life expectancy at birth was used as the sole indicator of population health. More recently, population health is also being expressed as healthy life expectancy and it is debated how healthy life expectancy will develop in the future. Since it is known that men and women have very different health and disease trajectories, we compared healthy life expectancy between the sexes, at birth and at age 80. From 1985 to 2010 life expectancy at birth in the Netherlands increased from 73.1 to 78.8 for men and from 79.7 to 82.7 for women. During the same period, the expected number of years without disabilities and in good self-reported health increased parallel, pointing to a shift of disability towards older age. Paradoxically, however, there has been an expansion of morbidity per se, as indicated by a continuing decrease in life expectancy without chronic diseases from 51.4 to 47.2 for men and from 48.8 to 40.6 for women. After these diverging trends of the last thirty years, Dutch women nowadays have a life expectancy that is 3.9 years longer than men but a life expectancy without chronic diseases that is 6.6 years lower. When examining these figures in the oldest old, the number of years expected to live in good health is similar for the sexes, but women of 80 years can expect to live another 9.7 years, still almost two years longer than the 7.9 years for men. All in all, the increase of life expectancy in the Netherlands is accompanied by a shift of disability but an expansion of morbidity, which is much more pronounced in women. It remains to be examined what biological or social mechanisms are behind these large sex differences in healthy life expectancy in the Netherlands. Show less
Engelaer F.M.; Bodegom D. van; Westendorp, R.G.J. 2013
Life expectancy has steadily increased with around 2.5 years per decade over the past 150 years and continuous to do so at a similar rate [1]. Before 1950, the increase in life expectancy was... Show moreLife expectancy has steadily increased with around 2.5 years per decade over the past 150 years and continuous to do so at a similar rate [1]. Before 1950, the increase in life expectancy was primarily driven by reductions in child mortality. During the last decades, however, the increase in life expectancy is mainly the result of mortality reductions at old age [2]. Better living conditions and hygiëne have saved us from an early death, while incremental health care innovations have brought us an old age Show less
Engelaer, Frouke M.; Bodegom, David van; Westendorp, Rudi G.J. 2012
Elder abuse has devastating consequences for older persons such as a poor quality of life, psychological distress, and loss of property and security. It is also associated with increased mortality... Show moreElder abuse has devastating consequences for older persons such as a poor quality of life, psychological distress, and loss of property and security. It is also associated with increased mortality and morbidity. Elder abuse is a problem that manifests itself in both rich and poor countries and at all levels of society. It is timely to discuss one of the basic problems that has hampered the study, detection and intervention of elder abuse as the variety of definitions that exist now produce a definitional chaos for researchers, practitioners, and policy makers. In this article we trace the elements of “how to define elder abuse” and situate them in their socio-historical context. We also analyze the purposes of these different definitions to assess their appropriateness in different settings concerned with elder abuse. Our analysis shows that elder abuse mirrors the societal arrangements which gave rise to them. It also highlights that it is a complex problem that is difficult to define. The central question is whether we need a common definition of elder abuse or different definitions that can be used in different settings. By evidence of our analysis we can see that there is a need for a sufficiently broad and flexible definition in order to cover different behaviors that can constitute abuse and the various settings in which it may occur. On the other hand, the definition needs to be specific and concrete to be useful in professional contexts. To take a further step forward for both research and practice of elder abuse, we propose to consistently adhere to the WHO definition that leads the enquirer towards a better understanding of the problem and helps to distinguish it from other phenomena; and to a simplified definition for professional practice that sets boundaries to the phenomena and is appropriate for effective prevention and intervention measures Show less
Zwiers, R.; Zantvoord, F.W.A.; Engelaer, F.M.; Bodegom, D. van; Ouderaa, F.J.G. van der; Westendorp, R.G.J. 2012
Objective To assess the mortality risk in subsequent years (adjusted for year of birth, nationality, and sex) of former Olympic athletes from disciplines with different levels of exercise intensity.
Engelaer, Frouke M.; Bodegom, David van; Westendorp, Rudi G.J. 2012
Goed opgeleide artsen in de zorgvragen van de komende decennia zijn in ons aller belang. Leyden Academy heeft, mede financieel gesteund door ZonMw in het kader van het Nationaal Programma... Show moreGoed opgeleide artsen in de zorgvragen van de komende decennia zijn in ons aller belang. Leyden Academy heeft, mede financieel gesteund door ZonMw in het kader van het Nationaal Programma Ouderenzorg, het initiatief genomen tot een inventarisatie van ouderengeneeskunde in de medische curricula. Het Raamplan 2009 met de eindtermen van de basisopleiding geneeskunde geeft een te summiere beschrijving van ouderengeneeskunde om gedegen onderwijs hierin te waarborgen. Dit is terug te zien in de voortgangstoetsen van studenten geneeskunde. Er is verspreid over de faculteiten goed onderwijs in ouderengeneeskunde, maar een compleet aanbod van theoretisch en praktisch onderwijs ontbreekt op de meeste faculteiten. Slechts op drie van de acht faculteiten is een hoogleraar ouderengeneeskunde in de tweede lijn. De werkgroep doet de volgende aanbevelingen: •Het raamplan dient te worden aangepast zodat alle studenten op gedegen wijze in de ouderengeneeskunde worden onderwezen, waarbij de begrippen in het hier opgestelde toetsingskader aan de orde moeten komen. •Alle studenten dienen in de bachelorfase theoretisch onderwijs over veroudering te krijgen en kennis te maken met de ouderengeneeskundige praktijk in een zorgstage. In de masterfase dienen zij bovendien te worden voorbereid op hun toekomstige praktijk door een verplicht coschap ouderengeneeskunde. •Om gedegen onderwijs in de ouderengeneeskunde op iedere faculteit te waarborgen dient op iedere faculteit een hoogleraar ouderengeneeskunde te worden aangesteld. Show less
De levensverwachting in Nederland is vanaf de 19e eeuw sterk toegenomen. Tot 1870 lag de gemiddelde levensverwachting beneden de 50 jaar,daarna begon de epidemiologische transitie, een overgang van... Show moreDe levensverwachting in Nederland is vanaf de 19e eeuw sterk toegenomen. Tot 1870 lag de gemiddelde levensverwachting beneden de 50 jaar,daarna begon de epidemiologische transitie, een overgang van sterfte door infectieziekten op jonge leeftijd naar sterfte door kanker en harten vaatziekten op hogere leeftijd. Deze transitie kan verklaard worden door verbeterde hygiëne, sociaal-economische ontwikkelingen en toegenomen medische kennis. Door deze ontwikkelingen is de kindersterfte vrijwel verdwenen en de gemiddelde levensverwachting fors gestegen. Op dit moment heeft een Nederlandse man een kans van 86 procent om de leeftijd van 65 jaar te bereiken en voor vrouwen is dit zelfs 90 procent. Daarbij is de levensverwachting voor mannen 77 jaar en voor vrouwen 81 jaar. Het resultaat van dit succes is dat er nu meer oude mensen zijn dan ooit te voren. Dat wil echter niet zeggen dat veroudering een nieuw fenomeen is. Ook in vroeger tijden waren er mensen die een hoge leeftijd bereikten, alleen waren er veel minder mensen die dit geluk mochten smaken. In dit hoofdstuk gaan we in op de factoren die de levensverwachting beïnvloeden, waarbij we ons concentreren op de rol die het immuunsysteem speelt gedurende de levensloop. Show less
Between 1934 and 1964, the Dutch repeatedly enjoyed the highest life expectancy in the world. Since then, both men and women experienced a long period of stagnation and by now life expectancy in... Show moreBetween 1934 and 1964, the Dutch repeatedly enjoyed the highest life expectancy in the world. Since then, both men and women experienced a long period of stagnation and by now life expectancy in the Netherlands has been surpassed by many countries. It has dropped from its first place position to the ninth place in the European Union (EU-15). As a longer life expectancy reflects the fact that good health is being maintained for longer, it is of key importance to better understand differences in life expectancy among countries. Show less
Kuningas, Maris; Bodegom, David van; May, Linda; Meij, Johannes J.; Slagboom, P. Eline; Westendorp, Rudi G.J. 2010
Various studies in mice have found support for the hypothesis that heterozygous carriers of cystic Wbrosis transmembrane conductance regulator (CFTR) mutations have an increased resistance to fatal... Show moreVarious studies in mice have found support for the hypothesis that heterozygous carriers of cystic Wbrosis transmembrane conductance regulator (CFTR) mutations have an increased resistance to fatal infection compared to both homozygous mutation carriers and non-carriers, while in humans such evidence is scarce. In this study, we assessed the CFTR heterozygotes survival advantage hypothesis in a contemporary rural population that lives under adverse environmental conditions in the Upper-East region of Ghana. We genotyped 30 SNPs throughout the CFTR gene in 4,230 participants and tested their inXuence on survival and on body composition in the population at large. With a sliding-window haplotype analysis, we identi- Wed a set of six common haplotypes that inXuenced survival probabilities (global p = 6.00 £ 10¡05). Individual haplotype analyses revealed two haplotypes of speciWc interest. One of these haplotypes was enriched (p = 0.003), whereas the other was depleted (p = 0.041) among people of old age (¸65 years) compared to young study participants (·5 years). In addition, children (n = 474) carrying the latter haplotype had lower body weight (ptrend = 0.020) and height (ptrend = 0.010) compared to non-carriers. For all these analyses, similar associations for heterozygous and homozygous CFTR haplotype carriers were observed, revealing an additive eVect of haplotype alleles. In conclusion, we identiWed common haplotypes in the CFTR gene that inXuence survival and body composition in the population at large with no evidence for heterozygote advantage. Show less
In a recent issue of this journal, Herndon [1] discussed the grandmother hypothesis and its implications for studies on cognitive ageing. According to this hypothesis, the long post-reproductive... Show moreIn a recent issue of this journal, Herndon [1] discussed the grandmother hypothesis and its implications for studies on cognitive ageing. According to this hypothesis, the long post-reproductive life span in human females is an adaptive mechanism that evolved to maximize female fitness by investing resources in the care of their grandchildren rather than by continuing to reproduce themselves. From this, Herndon deduces that special cognitive robustness to be maintained until after the age of menopause must have coevolved because grandmothers can only exert the beneficial effect if their cognitive abilities remain intact. He therefore pleas to compare cognitive ageing in humans with other primates, especially chimpanzees, because they lack a long post-reproductive life span and would therefore not have evolved this cognitive robustness. Here, we question the important role of grandmothers in our evolutionary past, first because of the different family structures during this time and second because of the low number of females that actually lived to experience a post-reproductive lifespan. We also show that in a population that reflects our evolutionary past, grandmothers do not have an important role for child survival. Finally, we react on the implications for the study of cognitive ageing as put forward by Herndon. Show less
May, Linda; Bodegom, David van; Frolich, Marijke; Lieshout, Lisette van; Slagboom, P Eline; Westendorp, Rudi GJ and Kuningas, Maris 2010
Toll-like receptors (TLRs) are involved in the induction of an adequate immune response on infection. We hypothesized that genetic variation in TLR4 and TLR2 genes could influence this response and... Show moreToll-like receptors (TLRs) are involved in the induction of an adequate immune response on infection. We hypothesized that genetic variation in TLR4 and TLR2 genes could influence this response and lead to variability in cytokine production and survival. We tested this hypothesis in 4292 participants who were followed up for all-cause mortality for 6 years and live under adverse environmental conditions in the Upper-East region of Ghana, where malaria is endemic. In 605 participants, tumor necrosis factor-a and interleukin-10 (IL10) production, after stimulation with lipopolysaccharide and zymosan, was measured. In addition, 34 single-nucleotide polymorphisms (SNPs) in TLR4 and 12 SNPs in TLR2 were genotyped and tested for association with cytokine production, malaria infection and mortality. In this comprehensive gene-wide approach, we identified novel SNPs in the TLR4 gene that influence cytokine production. From the analyzed SNPs, rs7860896 associated the strongest with IL10 production (P¼0.0005). None of the SNPs in this study associated with malaria or overall mortality risks. 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. Show less
May, Linda; Kuningas, Maris; Bodegom, David van; Meij, Hans J.; Frolich, Marijke; Slagboom, P. Eline; ... ; and Westendorp, Rudi G.J. 2009
Pentraxin 3 (PTX3) plays an important role in innate immune responses and in female fertility, as discovered with studies in mice. However, the role of PTX3 in human fertility is unknown. Here, we... Show morePentraxin 3 (PTX3) plays an important role in innate immune responses and in female fertility, as discovered with studies in mice. However, the role of PTX3 in human fertility is unknown. Here, we report on a population-based study from a rural area of Upper East Ghana (n ¼ 4346). We studied the association between the number of children given birth by women during their lifetime and ex vivo, lipopolysaccharide (LPS)-induced PTX3 production (n ¼ 362). In addition, we studied the association of genetic variation in the PTX3 gene with PTX3 production (n ¼ 617) and with female fertility (n ¼ 1999). We found that ex vivo LPS-induced PTX3 production was associated with fertility (P ¼ 0.040). Furthermore, we identified genetic variants in the PTX3 gene that influence PTX3 production, and also fertility. The strongest associations were observed for the rs6788044 single-nucleotide polymorphism (SNP). We found that carriers of this SNP had higher PTX3 production capacity (P ¼ 0.003) and higher fertility (P ¼ 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. Show less
May, Linda; Biggelaar, Anita HJ van den; Bodegom, David van; Meij, Hans J; Craen, Anton JM de; Amankwa, Joseph; ... ; Kuningas, Maris and Westendorp, Rudi GJ 2009
Background-: The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role... Show moreBackground-: The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether agerelated innate immune responses are similar or differ between populations living under very diverse environmental conditions. Methods-: We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304) and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562). Results-: We found a significant decrease in LPS-induced Interleukin (IL)-10 and Tumor Necrosis Factor (TNF) production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. 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. Show less
Bodegom, David van; May,Linda; Kuningas, Maris; Kaptijn, Ralf; Thomése, Fleur; Meij, Hans J.; ... ; Westendorp, Rudi G.J. 2009
Socio-economic status is an important determinant of health and survival in rural Africa and necessitates a practical and valid instrument to implement in health studies. Our objective was to... Show moreSocio-economic status is an important determinant of health and survival in rural Africa and necessitates a practical and valid instrument to implement in health studies. Our objective was to investigate the validity of the rapid appraisal method to assess socio-economic status and its ability to identify individuals at risk. Among 1573 households in rural northern Ghana, we calculated the Demographic Health Survey (DHS) wealth index and conducted two rapid appraisal methods: self-reported wealth and interviewer-reported wealth. In addition we followed the 25 184 participants from these households for survival with a mean follow-up of 3.9 years, during which 885 participants died. The DHS wealth index was moderately correlated to self-reported wealth (Spearman’s 0.59, P < 0.001) and interviewer-reported wealth (Spearman’s 0.75, P < 0.001). Mortality risks were significantly higher for people with lower than average self-reported wealth [hazard ratio (HR) 1.30 (95% CI 1.11—1.51)] and lower interviewerreported wealth [HR 1.40 (95% CI 1.21—1.62)]. Mortality risks were lower for people with higher self-reported wealth [HR 0.81 (95% CI 0.32—2.03)] and higher interviewer-reported wealth [HR 0.84 (95% CI 0.58—1.21)]. Similar discriminative mortality risks were assessed when using tertiles of the DHS wealth index (Ptrend < 0.001). Show less
