A millennium of population change in pre-modern Danish Ribe.

Denmark experienced major socioeconomic changes, including overall population growth, during the Viking, medieval and post-medieval periods from ca. AD 800 to 1800. Archaeological skeletons provide a unique perspective on the population structure of Ribe, a Danish town in Jutland, during the millennium that immediately precedes the industrialization of northern Europe. This skeletal study adds temporal depth to our understanding of an overall trend toward longer life as seen from historical records and in modern studies. Adult male and female mean age at death and mortality profiles during three time periods are based on 943 adult skeletons from three urban cemeteries that collectively represent a cross-section of this urban community. For both males and females, the mean age at death decreased slightly from the Viking (males 38.5 years, females 38.6 years) to the medieval (males 37.4 years, females 36.9 years) periods. This decline was followed by an increase in mean age at death for both sexes from the medieval to post-medieval (males 40.4 years, females 43.2 years) periods, a notable gain of 3.0 and 6.3 years for men and women, respectively.

Socio-demographic correlates of alcohol consumption in the Danish general population.

AIMS: Little is known about specific Danish drinking patterns. This paper investigates how various socio-demographic factors are related to Danish alcohol consumption with special focus on age and sex. METHODS: Data come from a national telephone survey of the Danish general population conducted in 2003 with a final sample size of 2,030 cases. Measures of beverage specific current drinking, overall drinking, daily drinking, heavy episodic drinking, mean consumption, volume per drinking occasion and frequency of drinking were analysed. RESULTS: A little over 5% of the population are abstainers. Fourteen per cent of men and 9% of women are heavy drinkers; 38% of men and 18% of women are heavy episodic drinkers. Youth of both sexes drink heavily, and especially in a binge drinking style. Regular, more temperate drinking is associated with increasing age. Multivariate analyses suggest that other than age and sex, classical socioeconomic factors do not play a great a role in determining drinking patterns. Social integrative factors in particular influence women's drinking. CONCLUSIONS: With respect to the rest of Europe and North America, Danes consume high levels of alcohol with a large percentage of youth drinking in a binge pattern. Classical socioeconomic factors play a lesser role in determining drinking patterns compared to other Western countries. Longitudinal studies and studies of alcohol-related consequences in the Danish general population should be conducted to better formulate alcohol and public health policy.

[Buffon, the director of 'Jardin du Roi' in the 1700s]. / Buffon, 1700-tallets leder af 'Jardin du Roi'--det medicinske fakultets konkurrent i Paris.

Buffon and Linné were the two greatest naturalists of the 1700s. As they were both born in 1707, their 300 anniversaries were therefore celebrated in France and Sweden. At the celebration meeting at the University of Bourgogne in Dijon - The Buffon Legacy - September 3-6, 2007, we presented the following paper: "Buffon and the longevity of species". In the present paper the life and work of Buffon is introduced on the basis of recent literature, including Jacques Roger's famous biography. Among non-biologists Buffon has nearly been forgotten, even though in the 1700s he was considered to be at the same level as the most famous French thinkers of the Enlightenment - Montesquieu, Voltaire, Rousseau and Diderot. His largest contributions were the publication of his comprehensive "Histoire naturelle" and his long and significant leadership of "Jardin du Roi", which he built up to become one of the best scientific institutions of Europe. Buffon's scientific contributions wereas overshadowed by those of Linné, as it was his classification system, which became dominant all overn Europe. Buffon's student Lamarck and later Darwin contributed by pushing Buffon in oblivion of history, even though Darwin valued him highly. However, in recent decades Buffon is experiencing a renaissance in connection with the increasing interest in biological anthropology, biogeography, ethology, and ecology, as well as on account of his modern species concept.

[Buffon and the longevity of species in the light of history]. / Buffon og arternes levealdre i historisk belysning.

In 1749 Buffon proposed a general law for the longevity of species. In retrospect this law laid the foundation for modern studies of correlations between biological variables. Buffon refers to "la durée totale de la vie", the maximum lifespan, and claims that there is a systematic relationship between this variable and a measure of the growth period. It transpires that Buffon believed that by multiplying the age at the termination of the growth period by 7 one obtains the maximum lifespan. In vol III o the supplements to "Histoire Naturelle" he presents a table with, i.a., age at first reproduction and maximum lifespan for 31 Mammalian species, Furthermore, he claims that the growth period is equivalent to 2 times the age at first reproduction. From Buffon's data, one obtains a mean ratio of approximately 13 between maximum lifespan and age at first reproduction, where the expected ratio is 14 (2x7), i.e. very close to the observed ratio. Inspired by Buffon's proposition, we have investigated the same relationship in a modern dataset, comprising 564 Mammalian species. The best fitting statistical model for the relationship is not a simple multiplication, but an allometric equation: maximum lifespan = 11.47x(age at first reproduction)0.65. Taking into account the variation due to, i.a., phylogenetic constraints and adaptive divergence, Buffon's idea represents a basic biological relationship between life history characters.

Genetic and environmental correlates of semen quality: a twin study.

BACKGROUND: The influences of environmental factors on the male reproductive system have been much debated over the last 3 decades. We studied the impact of genes and environment on semen quality, sex hormone levels, and sperm chromatin stability by using a twin design. METHODS: The study population consisted of monozygotic and dizygotic twins from the population-based Danish Twin Registry and a random selection of pairs of singleton brothers from the Danish Civil Registration System. All men were 20 to 45 years of age. The study population comprised 100 monozygotic twin brothers (50 pairs), 102 dizygotic twins (51 pairs), and 102 single-born brothers (51 pairs). A semen sample and blood sample were collected from all participants. RESULTS: Heritability was estimated to account for 20% (95% confidence interval = 0% to 68%) of the variation in sperm density. A higher heritability was found for the hormones reflecting Sertoli cell function (inhibin B, 76% [36% to 84%] and follicle-stimulating hormone, 81% [40% to 88%]) and for percent morphologic normal cells (41% [0% to 60%] and sperm chromatin parameters (mean alphaT, 68% [34% to 81%] and COMP alphaT, 72% [25% to 82%], respectively). CONCLUSION: Our study indicates a substantial hereditary component in plasma levels of hormones reflecting Sertoli cell function and in sperm cell chromatin stability and morphology. The environmental contribution (including the prenatal environment) appeared to be largest for sperm count.

No association between telomere length and survival among the elderly and oldest old.

BACKGROUND: The consistent findings of a negative correlation between telomere length and replicative potential of cultured cells, as well as a decreasing telomere length in a number of different tissues in humans with age, have led to the suggestion that telomeres play a role in cellular aging in vivo and ultimately even in organismal aging. Furthermore, one small longitudinal study of elderly individuals has suggested that longer telomeres are associated with better survival. METHODS: Telomere length was measured as mean terminal restriction fragment length on blood cells from 812 persons, age 73 to 101 years, who participated in population-based surveys in 1997-1998. Among the participants were 652 twins. The participants were followed up through the Danish Civil Registration system until January 2005, at which time 412 (51%) were dead. RESULTS: Univariate Cox regression analyses revealed that longer telomeres were associated with better survival (hazard ratios = 0.89 [95% confidence interval = 0.76-1.04] per 1 kb in males and 0.79 [0.72-0.88] per 1 kb in females, respectively). However, including age in the analyses changed the estimates to 0.97 (0.83-1.14) and 0.93 (0.85-1.03), respectively. Intrapair comparison showed that among 175 twin pairs in which at least one died during follow up, it was the twin with the shorter telomere length who died first in 97 (55%) of the pairs (95% confidence interval = 48-63%). We could not confirm the recently reported negative correlation between telomere length and obesity or between telomere length and smoking. CONCLUSION: This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for.

Telomere length among the elderly and oldest-old.

Human chromosomes terminate in a number of repeats of the sequence TTAGGG. At birth, each chromosome end is equipped with approximately 15 kb of telomere sequence, but this sequence is shortened during each cell division. In cell cultures telomere shortening is associated with senescence, a phenomenon that has also been observed in normal adult tissues, indicating that telomere loss is associated with organismal ageing. Previous work has established that the rate of telomere loss in humans is age dependent, and recent work shows a sex-specific difference in telomere length and shortening in individuals over the age span of 20 to 75 years. Here, terminal restriction fragment lengths on DNA purified from whole blood were measured to examine the mean telomere length in a cross-sectional cohort of 816 Danish individuals of age 73 to 101 years. In this age group, females show a linear correlation between telomere length and age, whereas the pattern tends to be nonlinear (quadratic in age) for males. This difference in telomere length dynamics between the 2 sexes may be caused by several different mechanisms, including differences in selection by mortality, differences in leukocyte population or different telomerase expression pattern.

The heritability of telomere length among the elderly and oldest-old.

A tight link exists between telomere length and both population doublings of a cell culture and age of a given organism. The more population doublings of the cell culture or the higher the age of the organism, the shorter the telomeres. The proposed model for telomere shortening, called the end replication problem, explains why the telomere erodes at each cellular turnover. Telomere length is regulated by a number of associated proteins through a number of different signaling pathways. The determinants of telomere length were studied using whole blood samples from 287 twin pairs aged 73 to 95 years. Structural equation models revealed that a model including additive genetic effects and non-shared environment was the best fitting model and that telomere length was moderately heritable, with an estimate that was sensitive to the telomere length standardization procedure. Sex-specific analyses showed lower heritability in males, although not statistically significant, which is in line with our earlier finding of a sex difference in telomere dynamics among the elderly and oldest-old.

Risk for multiple sclerosis in dizygotic and monozygotic twins.

We investigated the risks of twins for multiple sclerosis (MS). Our data are linked registers of all Danish twins and of all Danes born between 1920 and 1970 in whom MS was diagnosed before 1997. We compared differences in the risks for MS by Cox regression and standardized incidence ratios. Our analyses suggest that dizygotic twins have an approximately 60% lower risk for MS than monozygotic twins and a 20% lower risk than singletons. Monozygotic twins appear to have a somewhat higher risk for MS than singletons albeit not statistically significant. We offer no biological explanation for our findings, but suggest that either sharing fetal life with a genotypically different individual is beneficial for the immune system or that there is a linkage between the genes that influence dizygotic twinning and other genes that protect against MS.

Small effect of genetic factors on neck pain in old age: a study of 2,108 Danish twins 70 years of age and older.

STUDY DESIGN: Classic twin study. OBJECTIVES: To determine the heritability of neck pain in persons 70 years of age and older. SUMMARY OF BACKGROUND DATA: Previous studies have shown a moderate effect of genetic factors on back pain in the elderly. Genetic influence on neck pain in old age is unknown. METHODS: Data on the 1-month prevalence of neck pain from twin pairs participating in the population based Longitudinal Study of Aging Danish Twins formed the basis of this analysis. To assess twin similarity, probandwise concordance rates, odds ratios, and tetrachoric correlations were calculated and compared for monozygotic and dizygotic twins. Further, heritability estimates were calculated using bivariate probit estimation. RESULTS: A total of 2,108 twin individuals, including 1,054 complete twin pairs, answered the question related to neck pain at intake into the Longitudinal Study of Aging Danish Twins study. Low and nonsignificant probandwise concordance rates, odds ratios, and tetrachoric correlations were found for both men and women in monozygotic and dizygotic twin pairs, indicating small or negligible genetic effects. Heritability estimates adjusted for age and significant environmental risk factors (rheumatoid arthritis, osteoarthritis, disc prolapse, and coronary heart disease) showed no significant additive genetic, dominant genetic, or common environmental effects. CONCLUSION: Genetic factors do not play an important role in the liability to neck pain in persons 70 years of age or older.

The catalase -262C/T promoter polymorphism and aging phenotypes.

A low level of the central antioxidant enzyme catalase has been suggested to be a risk factor for diseases influenced by oxidative stress. In this study, we investigated the possible association of the catalase -262C/T polymorphism with survival, physical and cognitive functioning, and a number of oxidative stress-mediated disorders. The study population was 2223 Danish individuals, aged 45-93 years, drawn from three population-based surveys. The results suggest that the catalase -262C/T polymorphism is not associated with either survival, or the majority of the age-related phenotypes investigated. However, our data indicate a statistical significant association of TT homozygosity with improved physical functioning as well as a trend of the T allele conferring an improved general cognitive functioning, although these results did not remain significant after correcting for multiple testing. The results raise the hypothesis that the catalase -262T allele serves as protection against neurodegenerative and physical decline, although replication in other studies is warranted for confirmation of these findings.

Genetic and environmental contributions to back pain in old age: a study of 2,108 danish twins aged 70 and older.

STUDY DESIGN: Self-reported 1-month prevalence of back pain in older twins assessed at intake in a population-based longitudinal survey. OBJECTIVES: To determine the relative contribution of genetic and environmental factors to back pain in old age. SUMMARY OF BACKGROUND DATA: To date, genetic contributions to back pain in old age have not been assessed, to the authors' best knowledge. METHODS: Interview data given at entry into a nationwide cohort-sequential population-based survey of Danish twins aged 70 years and older in 1995, 1997, 1999, and 2001 form the basis of this analysis. Analysis of twin similarity was estimated using probandwise concordance rates, odds ratios, and tetrachoric correlations for back pain. Heritability (proportion of the population variance attributable to genetic variation) was estimated by bivariate probit estimation and adjusted for known significant environmental factors. Odds ratios for known environmental effects were estimated after controlling for age, sex, and genetic effects. RESULTS: Modest and nonsignificant differences between monozygotic and dizygotic twin pairs were found for probandwise concordance rates, odds ratios, and tet-rachoric correlations for both men and women. In the bivariate probit estimation, a current or previous diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse was found to significantly affect the risk of back pain. Additive genetic effects explained approximately one fourth of the liability to report back pain in men and none of the occurrence in women. Individual environmental effects were found to explain roughly 75% of the occurrence of back pain in men and 100% in women. CONCLUSIONS: Additive genetic effects are modest contributors to back pain in older men but not in women. A current or previous medical diagnosis of osteoporosis, degenerative joint disease, or lumbar disc prolapse is-strongly associated with back pain, also when genetic factors are controlled for. Because of inherent methodologic issues, this estimate of the genetic influence on back pain in old age is probably conservative.

[Werner Catel--a protagonist in Nazi "pediatric euthanasia" and his post-war career]. / Werner Catel--ein Protagonist der NS-"Kindereuthanasie" und seine Nachkriegskarriere.

This article deals with the biography of Werner Catel, a German paediatrician and protagonist of the Nazi programme for "euthanasia of children". Based on original research into recently discovered source materials, two aspects of Catel's life are considered. Firstly, Catel's attitude towards "euthanasia" is analysed. This analysis is not limited to the period of National Socialism, but focuses also on the phase before 1933 and especially on the era after 1945. Secondly, the authors explore Catel's academic career. What effects on his career in the later Federal Republic of Germany had his exposed role in the Nazi programme for "euthanasia of children"? In this context it is also examined how the Christian-Albrechts-University of Kiel/Germany, which employed Catel until 1960 in a leading position, judged the work of its former professor after his death.

Informational constraints on optimal sex allocation in ants.

Workers of the ant Formica truncorum specialize in rearing females or males depending on the number of fathers of a colony. These split sex ratios increase inclusive fitness, but it has remained unknown how workers assess the number of patrilines in their colonies and to what extent their reproductive decisions are constrained by lack of information. By analysis of the quantitative variation in cuticular hydrocarbon profiles of workers of multiply mated queens, we show that the heritable component of recognition cues is low and that the extent of sex ratio biasing toward males is correlated with patriline differences in hydrocarbon profiles. Workers are thus able to capitalize on colony-level relatedness asymmetry, but their inclusive fitness is constrained by uninformative recognition cues. These results are consistent with the hypothesis that the occasional expression of nepotistic phenotypes favoring full-sisters over half-sisters maintains selection against informative recognition cues. We evaluate how inclusive fitness theory may be used to predict the number and kind of recognition cues in insect societies of a specific relatedness structure.

Preliminary evidence of genetic anticipation in Graves' disease.

Despite strong epidemiologic evidence in favor of a genetic component in the etiology of Graves' disease, few hereditary risk factors have been consistently identified. The term genetic anticipation denotes a decrease in the age of onset as disease is passed through generations. In the past 5 years, genetic anticipation has been described in immune-mediated diseases such as rheumatoid arthritis and chronic inflammatory bowel disease, and recently this phenomenon has been linked to unstable expanded trinucleotide repeat sequences in several diseases. If present in Graves' disease, anticipation could provide clues to its genetic etiology. The aim of the present study was to investigate whether genetic anticipation may occur in Graves' disease. Age at diagnosis and age at ascertainment were registered and compared in 33 same-gender parent-offspring pairs with Graves' disease from multiply affected families primarily ascertained for a genetic linkage study. The mean age at diagnosis was 46.6 years (range, 16-77) in the parents and 34.1 years (range, 16-44) in the children. The difference in the mean age at diagnosis between parents and their children was 12.5 years (95% confidence interval 3.0-21.9), p = 0.010. Children were younger than their parents at diagnosis in 25 of 33 pairs (76%). In 7 pairs (21%), the parent was diagnosed after the child according to the calendar years. Essentially similar results were obtained after controlling for gender and smoking habits. In conclusion, our data suggest that patients in the second affected generation seem to acquire their disease at an earlier time in life in familial cases of Graves' disease, indicating that genetic anticipation might occur.

Hand grip strength: a phenotype suitable for identifying genetic variants affecting mid- and late-life physical functioning.

Physical functioning late in life has been shown to be affected by genetic factors. Only a few genetic variants have been suggested to be associated with physical functioning, and this only in selected populations (e.g., young healthy males and elite athletes). Declining physical functioning late in life is a major problem in terms of prevalence, morbidity, functional limitations, and quality of life. It is therefore of interest to find a phenotype reflecting physical functioning which has a relatively high heritability and which can be measured in large samples. Hand grip strength is known to be associated with muscular functioning in other muscle groups and with activities of daily living (ADL) functioning, and it predicts incident disability. We studied 1,757 Danish twin pairs aged 45-96 years, and found that this phenotype has a heritability of 52% (95% confidence interval (CI), 48-55%). A powerful design to detect genes associated with a phenotype is obtained using the extreme discordant and concordant sib pairs, of whom 28 and 77 dizygotic twin pairs, respectively, were found in this study. Hence grip strength is a suitable phenotype for identifying genetic variants of importance to mid- and late-life physical functioning.