Search

Background: Mortality rates have been reduced by half over the last 60 years for nonagenarians, and the progress is continuing. The greater survival might be due to overtreatment of severely physically and cognitively disabled individuals, which is a big concern for societies and individuals., Methods: The study population comprised two Danish birth cohorts: the 1905 Cohort and the 1915 Cohort. At age 95, all from the two cohorts who were still alive and living in Denmark were invited to participate in a health survey that used the same assessment instrument. A total of 2,670 (56.8%) persons participated in the two surveys and survival was assessed through a 7.3-year follow-up period during which 2,497 (93.5%) had died, and with virtually no loss to follow-up., Results: Despite the increasing chance of surviving to age 95, the 1915 Cohort had significantly better health and functioning than the 1905 Cohort. The survival advantage in the 1915 Cohort continued in the follow-up period after age 95: Median survival length was 2.4 months longer, p = .011. This advantage was not statistically associated with different levels of activities of daily living, physical performance, cognitive functioning, self-rated health and life satisfaction. However, the advantage tended to be more pronounced among people with better health., Conclusions: Life span and health increases among the oldest old. The improvement in survival for 95-year olds born in 1915 compared with 1905 was seen across the whole spectrum of health and functioning, with a tendency towards bigger improvement among those in good health., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: We aim to shed light on progress in cancer medicine through studying time trends in age-specific rates of cancer incidence and mortality over the last quarter century., Methods: We analyzed age-specific incidence and mortality rates of all cancer sites combined using the high-quality population-based databases of Denmark, Finland, Norway, Sweden, and the Netherlands for the period 1990-2016., Results: Over these 26 years, cancer incidence rates increased in all investigated countries irrespective of age by about 22%. By contrast, cancer mortality rates decreased across all ages, also by about 22%, except ages 80+ years in Denmark, Norway, and Sweden, where they remained unchanged. This pattern is consistent with earlier diagnoses and more effective treatments of cancer., Conclusions: This bird's-eye view on cancer reveals substantive progress in cancer medicine., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The adverse association between income, health and survival is well documented, but little is known about how income trajectories influence health and survival for men and women. We aim to investigate sex differences in mortality and hospitalisations by income and income changes., Methods: We performed a population-based, nationwide study including 1 063 787 Danes born 1935-1955 and residing in Denmark during 1980-2015. Income was calculated during two age intervals: 45-49 and 55-59 years. The average income was divided into quartiles for men and women separately, which formed the basis for the income trajectories. Individuals were followed up from age 60 until 2014/2015 for hospital admission and mortality, respectively., Results: Men had higher mortality and were more hospitalised than women. Sex differences in mortality were most pronounced for people with stable low income (relative difference in hazard=1.93; 95% CI 1.89 to 1.98) and a downward income trajectory (1.91; 95% CI 1.85 to 1.98) with smaller sex differences for people with an upward trajectory (1.59; 95% CI 1.56 to 1.62) and stable high income (1.37; 95% CI 1.33 to 1.41). A similar pattern was found for family income. Regarding hospitalisations, similar results were found, though less pronounced. Investigation of mortality and hospitalisations by all possible trajectories demonstrated that income at ages 55-59 was an important predictor of mortality, with increasing mortality for decreasing income quartile., Conclusion: Income trajectories as a proxy for change in social position have a larger influence on men's than women's health and mortality. Income in the late 50s is an important predictor of mortality, particularly for men., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

The number of very old individuals in the population is rapidly increasing. Previous studies have indicated that many factors known to be strongly associated with survival among middle-aged and elderly show no association among the oldest old. Resting heart rate (RHR) is associated with increased risk of death in the general population as well as in patients with various types of heart disease. The association between RHR and mortality in the very old is the subject of this report. The study population was identified in The Nationwide Danish 1905 Cohort Study ( n  = 1086) and comprised 854 subjects with a median age of 95.2 years (range 94.7-95.9), in whom RHR was measured by radial pulse palpation. Participants were followed until death through the civil registration system, and remaining lifespan after RHR measure was used as outcome. Participants were divided into six groups according to RHR (≤50, 51-60, 61-70, 71-80, 81-90 and ≥91) with the largest group used as the reference group (61-70 beats per minute (bpm)). Survival analyses using Cox' proportional hazards models were performed to study the association between RHR and mortality. Median RHR was 68 bpm in males (IQR 62-76) and 70 bpm (IQR 64-78) in females. After stratifying both sexes into six groups according to RHR, we found no significant difference in remaining lifespan between groups in either males or females. No significantly increased risk was demonstrated in groups with higher RHR. In very old people, elevated RHR is not associated with increased mortality.

Background: This study investigates the accuracy of the reporting of medication use by proxy- and self-respondents, and it compares the prognostic value of the number of medications from survey and registry data for predicting mortality across self- and proxy-respondents., Methods: The study is based on the linkage of the Longitudinal Study of Aging Danish Twins and the Danish 1905-Cohort Study with the Danish National Prescription Registry. We investigated the concordance between survey and registry data, and the prognostic value of medication use when assessed using survey and registry data, to predict mortality for self- and proxy-respondents at intake surveys., Results: Among self-respondents, the agreement was moderate (κ = 0.52-0.58) for most therapeutic groups, whereas among proxy-respondents, the agreement was low to moderate (κ = 0.36-0.60). The magnitude of the relative differences was, generally, greater among proxies than among self-respondents. Each additional increase in the total number of medications was associated with 7%-8% mortality increase among self- and 4%-6% mortality increase among proxy-respondents in both the survey and registry data. The predictive value of the total number of medications estimated from either data source was lower among proxies (c-statistic = 0.56-0.58) than among self-respondents (c-statistic = 0.74)., Conclusions: The concordance between survey and registry data regarding medication use and the predictive value of the number of medications for mortality were lower among proxy- than among self-respondents., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Objectives: We examine the mortality of men and women within the first year after all-cause and cause-specific hospital admission to investigate whether the sex differences in mortality after hospitalisation are higher than in the corresponding general and non-hospitalised population., Design: This is a population-based, longitudinal study with nationwide coverage. The study population was identified by linking the National Patient Register with the Central Population Register using a 5% random sample of the Danish population., Setting: The population born between 1898 and 1961, who was alive and residing in Denmark after 1977, was followed up between 1977 and 2011 with respect to hospital admissions and mortality while aged 50-79., Primary Outcome Measures: The absolute sex differences in the 1-year risk of dying after all-cause and cause-specific hospital admission. The hospitalised population sex differentials were then compared with the sex differences in a general and a non-hospitalised population, randomly matched by age, sex and hospitalisation status., Results: The risk of dying was consistently higher for hospitalised men and women. At all ages, the absolute sex differences in mortality were largest in the hospitalised population, were smaller in the general population and were smallest in the non-hospitalised population. This pattern was consistent across all-cause admissions, and with respect to admissions for neoplasms, circulatory diseases and respiratory diseases. For all-cause hospital admissions, absolute sex differences in the 1-year risk of dying resulted in 43.8 excess male deaths per 1,000 individuals within the age range 50-79, while the levels were lower in the general and the non-hospitalised population, at levels of 13.5 and 6.6, respectively., Conclusions: This study indicates a larger male disadvantage in mortality following hospitalisation, pointing towards an association between the health status of a population and the magnitude of the female advantage in mortality., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study compares handgrip strength and its association with mortality across studies conducted in Moscow, Denmark, and England., Materials: The data collected by the Study of Stress, Aging, and Health in Russia, the Study of Middle-Aged Danish Twins and the Longitudinal Study of Aging Danish Twins, and the English Longitudinal Study of Ageing was utilized., Results: Among the male participants, the age-standardized grip strength was 2 kg and 1 kg lower in Russia than in Denmark and in England, respectively. The age-standardized grip strength among the female participants was 1.9 kg and 1.6 kg lower in Russia than in Denmark and in England, respectively. In Moscow, a one-kilogram increase in grip strength was associated with a 4% (hazard ratio [HR] = 0.96, 95% confidence interval [CI]: 0.94, 0.99) reduction in mortality among men and a 10% (HR = 0.90, 95%CI: 0.86, 0.94) among women. Meanwhile, a one-kilogram increase in grip strength was associated with a 6% (HR = 0.94, 95%CI: 0.93, 0.95) and an 8% (HR = 0.92, 95%CI: 0.90, 0.94) decrease in mortality among Danish men and women, respectively, and with a 2% (HR = 0.98, 95%CI: 0.97, 0.99) and a 3% (HR = 0.97, 95%CI: 0.95, 0.98) reduction in mortality among the English men and women, respectively., Conclusion: The study suggests that, although absolute grip strength values appear to vary across the Muscovite, Danish, and English samples, the degree to which grip strength is predictive of mortality is comparable across national populations with diverse socioeconomic and health profiles and life expectancy levels.

An epigenetic profile defining the DNA methylation age (DNAm age) of an individual has been suggested to be a biomarker of aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm age of 378 Danish twins, age 30-82 years, and furthermore included a 10-year longitudinal study of the 86 oldest-old twins (mean age of 86.1 at follow-up), which subsequently were followed for mortality for 8 years. We found that the DNAm age is highly correlated with chronological age across all age groups (r = 0.97), but that the rate of change of DNAm age decreases with age. The results may in part be explained by selective mortality of those with a high DNAm age. This hypothesis was supported by a classical survival analysis showing a 35% (4-77%) increased mortality risk for each 5-year increase in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed a more-than-double mortality risk for the DNAm oldest twin compared to the co-twin and a 'dose-response pattern' with the odds of dying first increasing 3.2 (1.05-10.1) times per 5-year DNAm age difference within twin pairs, thus showing a stronger association of DNAm age with mortality in the oldest-old when controlling for familial factors. In conclusion, our results support that DNAm age qualifies as a biomarker of aging., (© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

One method by which to identify fundamental biological processes that may contribute to age-related disease and disability, instead of disease-specific processes, is to construct endophenotypes comprising linear combinations of physiological measures. Applying factor analyses methods to phenotypic data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2 cohorts. Thus, this endophenotype construct may represent an underlying phenotype related to aging. Additional genetic studies of this endophenotype may help identify genetic variants or networks that contribute to the aging process., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In high income countries females outlive men, although they generally report worse health, the so-called male-female health-survival paradox. Russia has one of the world's largest sex difference in life expectancy with a male disadvantage of more than 10 years. We compare components of the paradox between Denmark and Moscow by examining sex differences in mortality and several health measures. The Human Mortality Database and the Russian Fertility and Mortality Database were used to examine sex differences in all-cause death rates in Denmark, Russia, and Moscow in 2007-2008. Self-reported health data were obtained from the Study of Middle-Aged Danish Twins (n = 4,314), the Longitudinal Study of Aging Danish Twins (n = 4,731), and the study of Stress, Aging, and Health in Russia (n = 1,800). In both Moscow and Denmark there was a consistent female advantage at ages 55-89 years in survival and a male advantage in self-rated health, physical functioning, and depression symptomatology. Only on cognitive tests males performed similarly to or worse than women. Nevertheless, Muscovite males had more than twice higher mortality at ages 55-69 years compared to Muscovite women, almost double the ratio in Denmark. The present study showed that despite similar directions of sex differences in health and mortality in Moscow and Denmark, the male-female health-survival paradox is very pronounced in Moscow suggesting a stronger sex-specific disconnect between health indicators and mortality among middle-aged and young-old Muscovites.

Background: Surfactant protein D (SP-D) is produced in the lungs and additional mucosal surfaces. Systemic SP-D levels are previously associated to aging-related- and lifestyle-related disorders and predicts mortality in cardiovascular and lung diseases. However, the association between higher serum SP-D levels and mortality in the general population is unknown. We hypothesized that increased systemic levels of SP-D may be used as prognostic factor for assessing the mortality in the elderly., Methods and Results: SP-D serum levels were measured in 689 elderly subjects and mortality ratios were investigated after a 13-year follow-up period. Survival analysis showed that increasing quartiles of serum SP-D levels were associated to mortality in 70+ year old women (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.93-1.78; p = 0.032) adjusted for age, smoking and BMI. Women with SP-D levels above 2100 ng/ml had significantly increased mortality when compared to elderly women with SP-D levels equal to or below 2100 ng/ml (HR, 1.45; 95% CI, 1.12-1.88; p = 0.005). The likelihood that the female twin with the highest SP-D level died first increased with increasing SP-D levels (p = 0.031) - that is, the bigger intra-pair difference in SP-D level, the higher the probability that the twin with the highest measure died first (odds ratio [OR], 1.66; p = 0.047)., Conclusion: The study demonstrates that higher circulating SP-D levels are associated with increased mortality rate in elderly women in this population-based cohort study. SP-D may serve as a biomarker to track the cardio-pulmonary health status in elderly women., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

In mammalian females, one of the two X chromosomes is inactivated in early embryonic life. Females are therefore mosaics for two cell populations, one with the maternal and one with the paternal X as the active X chromosome. A skewed X inactivation is a marked deviation from a 50:50 ratio. In populations of women past 55-60 years of age, an increased degree of skewing (DS) is found. Here the association between age-related skewing and mortality is analyzed in a 13-year follow-up study of 500 women from three cohorts (73-100 years of age at intake). Women with low DS had significantly higher mortality than the majority of women who had a more skewed DS (hazard ratio: 1.30; 95% CI: 1.04-1.64). The association between X inactivation and mortality was replicated in dizygotic twin pairs for which the co-twin with the lowest DS also had a statistically significant tendency to die first in the twin pairs with the highest intra-pair differences in DS (proportion: 0.71; 95% CI: 0.52-0.86). Both results suggest that lower DS is associated with higher mortality. We therefore propose that age-related skewing may be partly due to a population selection with lower mortality among those with higher DS.

Schooling generally is positively associated with better health-related outcomes-for example, less hospitalization and later mortality-but these associations do not measure whether schooling causes better health-related outcomes. Schooling may in part be a proxy for unobserved endowments-including family background and genetics-that both are correlated with schooling and have direct causal effects on these outcomes. This study addresses the schooling-health-gradient issue with twins methodology, using rich data from the Danish Twin Registry linked to population-based registries to minimize random and systematic measurement error biases. We find strong, significantly negative associations between schooling and hospitalization and mortality, but generally no causal effects of schooling.

To disentangle an independent effect of educational status on mortality risk from direct and indirect selection mechanisms, the authors used a discordant twin pair design, which allowed them to isolate the effect of education by means of adjustment for genetic and environmental confounding per design. The study is based on data from the Danish Twin Registry and Statistics Denmark. Using Cox regression, they estimated hazard ratios for mortality according to the highest attained education among 5,260 monozygotic and 11,088 dizygotic same-sex twin pairs born during 1921-1950 and followed during 1980-2008. Both standard cohort and intrapair analyses were conducted separately for zygosity, gender, and birth cohort. Educational differences in mortality were demonstrated in the standard cohort analyses but attenuated in the intrapair analyses in all subgroups but men born during 1921-1935, and no effect modification by zygosity was observed. Hence, the results are most compatible with an effect of early family environment in explaining the educational inequality in mortality. However, large educational differences were still reflected in mortality risk differences within twin pairs, thus supporting some degree of independent effect of education. In addition, the effect of education may be more pronounced in older cohorts of Danish men.

The present study aims to compare the direction and magnitude of sex differences in mortality and major health dimensions across Denmark, Japan and the US. The Human Mortality Database was used to examine sex differences in age-specific mortality rates. The Danish twin surveys, the Danish 1905-Cohort Study, the Health and Retirement Study, and the Nihon University Japanese Longitudinal Study of Aging were used to examine sex differences in health. Men had consistently higher mortality rates at all ages in all three countries, but they also had a substantial advantage in handgrip strength compared with the same-aged women. Sex differences in activities of daily living (ADL) became pronounced among individuals aged 85+ in all three countries. Depression levels tended to be higher in women, particularly, in Denmark and the HRS, and only small sex differences were observed in the immediate recall test and Mini-Mental State Exam. The present study revealed consistent sex differentials in survival and physical health, self-rated health and cognition at older ages, whereas the pattern of sex differences in depressive symptoms was country-specific.

Background: In the call for papers (Alley DE, Ferrucci L, Barbagallo M, Studenski SA, Harris TB. A research agenda: the changing relationship between body weight and health in aging. J Gerontol A Biol Sci Med Sci. 2008;63(11):1257-1259.), it is assumed that the association between body mass index (BMI [kilogram per square meter]) and mortality becomes increasingly U-shaped with advancing age. The aim of this study is to examine the association between BMI and mortality and to test whether the association is changing with advancing age for persons aged 70-95 years in Denmark., Methods: The study populations comprised two surveys: the Longitudinal Study of Aging of Danish Twins (LSADT) and the Danish 1905 Cohort Survey. From 1995 to 1999, 4253 individuals aged 70-95 years from the LSADT were interviewed at home. In 1998, 2,262 individuals aged 92-93 years from the 1905 Cohort were interviewed at home. The information in both surveys included self-reported weight and height. With virtually no loss to follow-up, survival was assessed through a 10-year follow-up period, during which 4,664 (72%) of the persons died., Results: The association between BMI and mortality is changing with advancing age for people aged 70-95 years. There was a significant decrease in the association between mortality and low BMI with advancing age for both genders (p < or = .03). There was also a tendency for the association between mortality and high BMI to decrease with advancing age for males (p = .06)., Conclusion: In a large contemporary Danish population-based sample, the association of BMI and mortality became decreasingly U-shaped with advancing age for the age range 70-95 years.

Background/aims: Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are widely used markers of liver disease. Several population-based cohort studies have found associations of these liver enzymes with all-cause mortality. None of these studies controlled for genetic variation as well as fetal and early life exposure, whether environmental or genetic., Methods: We studied the associations of ALT and GGT with all-cause mortality using data for 686 twins (73-94 years old) included in the Longitudinal Study of Aging Danish Twins., Results: An increase in 1 logged U/L of GGT was associated with a 15% increase in the hazard ratio (HR) for mortality [95% confidence interval (CI) 0.99, 1.32] but there was no strong evidence of an association of ALT with all-cause mortality (HR=1.07, 95% CI 0.82, 1.40) when controlling for potential confounders. In this analysis, the study population was treated as individuals, with similarities between twins accounted for by using robust standard errors. However, an intrapair analysis in which the proportion of twin pairs in which the twin with the higher level of ALT or GGT died first was compared with 50% (expected under the null hypothesis), found no strong evidence that higher ALT or GGT was associated with earlier death within twin pairs; the results were consistent in both monozygotic and dizygotic twins., Conclusions: gamma-glutamyltransferase but not ALT predicts mortality among older Danish twins when using traditional methods for controlling for potential confounders and existing diabetes and cardiovascular disease. Environmental developmental origins may explain the association, but larger twin studies are required to replicate our findings.

We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather indicators, and demographic indicators. We argue that these features can only affect high-age mortality by way of the individual early-life conditions. Moreover, they are exogenous from the individual point of view, which is a methodological advantage compared to the use of unique characteristics of the newborn individual or his or her family or household as early-life indicators. We collected national annual time-series data on the above-mentioned indicators, and we combine these to the individual data records from the Danish Twin Registry covering births in 1873-1906. The empirical analyses (mostly based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life.

Objectives: To examine duration of sickness absence as a risk marker for future mortality by socio-economic position among all private sector employees in Denmark in 1998-2004., Methods: All residents in Denmark employed in the private sector receiving sickness absence compensation in 1998 were investigated in a prospective cohort study. 236 207 persons (38.2% women, 61.8% men, age range 18-65, mean age 37.8 years) alive on 1 January 2001 were included in the study. Mortality from 1 January 2001 to 31 December 2004 was assessed using national register data. Deaths in 1999 and 2000 were excluded to determine the status of sickness absence duration as an early risk marker. For analyses within occupational grades, data were available for a sub-population of 137 607 study participants., Results: 3040 persons died during follow-up. The age-adjusted risk of future mortality increased by duration of sickness absence in a graded fashion among men and non-blue collar workers. Among women and blue collar workers, there was no association of mortality with duration of sickness absences below 6 weeks. However, employees with > or =6 weeks of absence compared to those with 1-week absence had a substantial excess risk of death in all groups: adjusted hazard ratio 2.2 (95% CI 1.8 to 2.7) for women, 2.1 (95% CI 1.8 to 2.4) for men, 3.7 (95% CI 1.9 to 7.2) in white collar occupations, 3.3 (95% CI 2.2 to 5.0) in intermediate grade occupations and 2.0 (95% CI 1.7 to 2.3) in blue collar occupations., Conclusion: Administratively collected data on sickness absence compensation for periods > or =6 weeks identified "at risk" groups for future excess mortality in male and female private sector employees across occupational grade levels.

Leukocyte telomere length, representing the mean length of all telomeres in leukocytes, is ostensibly a bioindicator of human aging. The authors hypothesized that shorter telomeres might forecast imminent mortality in elderly people better than leukocyte telomere length. They performed mortality analysis in 548 same-sex Danish twins (274 pairs) aged 73-94 years, of whom 204 pairs experienced the death of one or both co-twins during 9-10 years of follow-up (1997-2007). From the terminal restriction fragment length (TRFL) distribution, the authors obtained the mean TRFL (mTRFL) and the mean values of the shorter 50% (mTRFL(50)) and shortest 25% (mTRFL(25)) of TRFLs in the distribution and computed the mode of TRFL (MTRFL). They analyzed the proportions of twin pairs in which the co-twin with the shorter telomeres died first. The proportions derived from the intrapair comparisons indicated that the shorter telomeres predicted the death of the first co-twin better than the mTRFL did (mTRFL: 0.56, 95% confidence interval (CI): 0.49, 0.63; mTRFL(50): 0.59, 95% CI: 0.52, 0.66; mTRFL(25): 0.59, 95% CI: 0.52, 0.66; MTRFL: 0.60, 95% CI: 0.53, 0.67). The telomere-mortality association was stronger in years 3-4 than in the rest of the follow-up period, and it grew stronger with increasing intrapair difference in all telomere parameters. Leukocyte telomere dynamics might help explain the boundaries of the human life span.

This review examines sex differences in health and survival, with a focus on the Nordic countries. There is a remarkable discrepancy between the health and survival of the sexes: men are physically stronger and have fewer disabilities, but have substantially higher mortality at all ages compared with women: the so-called male-female health-survival paradox. A number of proposed explanations for this paradox are rooted in biological, social, and psychological interpretations. It is likely to be due to multiple causes that include fundamental biological differences between the sexes such as genetic factors, immune system responses, hormones, and disease patterns. Behavioral differences such as risk-taking and reluctance to seek and comply with medical treatment may also play a role. Another consideration is that part of the difference may be due to methodological challenges, such as selective non-participation and under-reporting of health problems, and delayed seeking of treatment by men. The Nordic countries provide a unique opportunity for such studies, as they have good-quality data in their national health registers, which cover the whole population, and a long tradition of high participation rates in surveys.

Objective: Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades., Methods: Age-period-cohort study of mortality for all Danish women and men aged 79-98 during the period 1949-2006., Outcome Measures: Relative risks for deaths and second order differences for exploration of the nonlinear variation., Results: Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models., Conclusions: Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects.

Introduction: The study examines sex mortality differences in Denmark 1840-2005 with focus on time trends., Materials and Methods: The material is based on cause of death statistics. The mortality is expressed for men and women by life expectancy and age and cause specific mortality rates., Results: Since 1840 life expectancy has increased for both sexes, and Danish women have constantly had a longer life expectancy than Danish men. Until 1950 the difference was 2-3 years, but then the difference increased to 6 years and is now about 4 years. Since 1900 the mortality rate for children below one year of age has constantly been 20-40% higher among boys than among girls. From 1900 until 1950 only a minor sex difference was seen among adults, but then substantial sex differences appeared. Since 1920 there have only been minor sex differences for deaths due to influenza, infections and colorectal cancer. For heart diseases, diabetes and stroke the male excess mortality increased. For deaths related to smoking and alcohol great changes in sex differences have appeared since 1950, likewise for suicide, traffic accidents and accidental poisonings., Conclusion: In the last 160 years Danish women have had a longer life expectancy than Danish men. Notable changes in sex difference in life expectancy in the last 50 years can mainly be attributed to diseases and causes of deaths closely related to life style and health behaviour interacting with living conditions.

New Danish data from the Health and Morbidity Survey 2005 confirm the male/female paradox with regard to health and survival: men have, in general, the best health indicators (with cardiovascular diseases as the most important exception), but women live longer. The reason for this paradox is undoubtedly multifactorial with biological (hormonal, immunological, genetic), behavioural (smoking, risk behaviour, sickness behaviour), and social (the male role) factors.

The rapid increase in twinning rates in developed countries has increased interest in the question as to whether twin mothers have higher mortality and more health problems than mothers of singletons. Here we use a national survey, the Office for National Statistics Longitudinal Study of England & Wales, and a linkage between the Danish Twin Registry and the Danish population register to examine mortality patterns after age 45 (50 for fathers) for twin parents and the whole population born from 1911 to 1950. For England and Wales, presence of limiting long-term illnesses and self-rated health status was also investigated. Overall similar health and mortality was found for twin parents and the whole population although both life table methods and survival analysis suggested a slight excess mortality among older cohorts of twin mothers in England and Wales.

Purpose: We examined whether the presence of a spouse and the frequency of interaction with children, relatives, and friends significantly influence the risk of dying in late life. We assessed these effects separately by gender, controlling for self-reported health. In addition, we examined whether interaction with the co-twin has a different impact on mortality for identical and fraternal twins., Design and Methods: The data set consists of 2,147 Danish twins aged 75 years and older, who were followed prospectively from 1995 to 2001. We modeled the effect of social ties on mortality by using event history analysis., Results: Survival is extended by having a spouse and close ties with friends and the co-twin. However, contact frequency with friends and the co-twin is significant, respectively, only for women and identical twins., Implications: Investigating social relations sheds light on the life span of individuals older than 75 years of age. We stress the importance of social relations beyond the presence of the spouse for survival even at very old ages.

Objectives: : To elucidate whether well-known predictions of mortality are reduced or even reversed, or whether mortality is a stochastic process in the oldest old., Design: : A multidimensional survey of the Danish 1905 cohort conducted in 1998 with follow-up of vital status after 15 months., Setting: : Denmark., Participants: : All Danes born in 1905, irrespective of physical and mental status were approached. Two thousand two hundred sixty-two persons of 3,600 participated in this survey., Measurements: : Professional interviewers collected data concerning sociodemographic factors, smoking, alcohol consumption, body mass index, physical and cognitive performance, and health during a visit at the participant's residency. Cox regression models were used to evaluate predictors of mortality., Results: : Five hundred seventy-nine (25.7%) of the 2,249 participants eligible for the analysis died during the 15 months follow-up. Multivariate analyses showed that marital status, education, smoking, obesity, consumption of alcohol, and number of self-reported diseases were not associated with mortality. Disability and cognitive impairment were significant risk factors in men and women. In addition poor self-rated health was associated with an increase in mortality in women., Conclusion: : In the oldest old, several known predictors of mortality, such as sociodemographic factors, smoking, and obesity, have lost their importance, but a high disability level, poor physical and cognitive performance, and self-rated health (women only), predict mortality, which shows that mortality in the oldest old is not a stochastic process.

Purpose: Studies of younger individuals have suggested an association between ACE genotype and physical and cognitive performance. Using a longitudinal study of elderly twins we studied the association between ACE genotype and physical and cognitive functioning and survival in old age., Methods: Participants were 684 twins aged 73+ years from the 1997 and 1999 surveys of the Longitudinal Study of Aging Danish Twins. Cognitive skills were assessed by the MMSE, while physical abilities were determined through self-report in 1997 and through both self-report and measurement of performance in two physical tasks in 1999. Survival status was obtained through linkage with a national death register., Results: Neither physical nor cognitive performance was associated with ACE genotype at baseline in 1997, or at follow-up in 1999. For participants in both surveys longitudinal changes in these skills did not depend on ACE genotype. The relative risk of dying was increased in II compared with the DI and DD genotype with relative risks of 1.6 (95 percent confidence intervals 1.1-2.5) and 1.3 (0.8-2.1), respectively., Conclusion: We found no substantial effects of ACE genotype on physical and cognitive performance, or rate of change among elderly. Persons with the D allele may have a lower mortality at older ages.

Several studies have explored the impact of marital bereavement on mortality, while increasing emphasis has recently been placed on genetic factors influencing longevity - in this paper, we study the impact of losing the spouse and losing the co-twin, for twins aged 50 to 70. We use data from the Danish Twin Registry and the Population Register of Denmark for the period 1968 through 1999. Firstly, we use survival analysis to study mortality after the death of the spouse or the co-twin. We find that the risk of dying is highest in the first year after the death of the spouse, as well as in the second year after the death of the co-twin. We then use event history analysis techniques to show that there is a strong impact of the event 'losing the co-twin' even after controlling for age, sex and zygosity and that this effect is significantly higher in the second year of bereavement. The effect is similar for men and women, and it is higher for monozygotic twins. The latter confirms the influence of genetic factors on survival, while the mortality trajectory with a peak in the second year after the death of the co-twin is consistent with the existence of a twin bereavement effect.

Despite differences in research traditions, the disciplines of genetics, epidemiology, and demography are becoming increasingly integrated in health-related research. The enormous development within genetic technology, with the possibility of genotyping thousands of variants from small samples of biological material obtained by non-invasive methods, now makes it feasible to include genetic information in epidemiologic and demographic studies. Simultaneously, new insight can be obtained from hybrids of methods and data from the three disciplines. This paper illustrates how a genetic observation combined with demographic insight and a modified genetic-epidemiologic design (a twin study) provides evidence that part of the sex difference in survival can be attributed to the fact that females have two X chromosomes and males have only one, a result that is of potential interest for genetics, epidemiology, and demography.

The declining prevalence of left-handed individuals with increasing age has led to two main avenues of hypotheses; the association is due either (1) to a birth cohort effect and/or an age effect caused by a switch to right-handedness with advancing age or (2) to mortality selection that reduces survival in left-handed individuals, or both. It is uncertain whether a cohort or age effect can explain the decline in age-related prevalence, and conflicting evidence exists in favor of the mortality hypothesis. We compared mortality in a subgroup of 118 opposite-handed twin pairs by counting in how many instances the right-handed twin died first. There was no evidence of differential survival between right-handed and non-right-handed individuals in the entire 1900-1910 cohort. With respect to the number of right-handed twins who died first, there was no material disadvantage among those who were not right-handed. In 60% (95% confidence interval = 49.0-71.5%) of dizygotic pairs, the right-handed twins died first. In 50% of monozygotic pairs, right-handed twins died first. The prevalence of not being right-handed was higher among males (9.2%) than females (6.5%); there was a similar frequency of non-right-handedness in monozygotic (8.0%) and dizygotic (7.8%) twins. We did not find evidence of excess mortality among non-right-handed adult twins in this follow-up study.

Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correlation of death rates across age, individual differences in survival chances, and induced alterations in age patterns of fertility and mortality--offer clues and suggest research on the failure of complicated systems, on new demographic equations for evolutionary theory, and on fertility-longevity interactions. Nongenetic changes account for increases in human life-spans to date. Explication of these causes and the genetic license for extended survival, as well as discovery of genes and other survival attributes affecting longevity, will lead to even longer lives.

Nutrition early in life may influence adult mortality. The fetal-origins hypothesis suggests that nourishment before birth and during the individual's infancy programs the development of risk factors for several important diseases of middle and old age. The present study was designed to evaluate the impact of extreme nutritional deprivation in utero and during infancy and early childhood on mortality in later life. The authors analyzed the survival of the cohorts born in Finland during the severe 1866-1868 famine and during the 5 years immediately preceding and 5 years immediately following the famine. The study included 331,932 individuals born prior to the famine, 161,744 born during the famine, and 323,321 born after the famine. The authors assessed survival by cohorts from birth to age 17 years and from age 17 to 40, 60, and 80 years, as well as average length of life after age 80 years. Survival from birth to age 17 years was significantly lower in cohorts born before and during the famine than in the cohorts born after the famine (males, 0.566 vs. 0.671, a difference of 0.105 (95% confidence interval (CI) 0.102-0.108); females, 0.593 vs. 0.692, a difference of 0.099 (95% CI 0.096-0.102)). At subsequent ages, including old age, mortality was practically identical in the famine-born cohorts and in the five cohorts born before and after the crisis. For both males and females, survival from 17 to 80 years and mean remaining lifetime at age 80 years were very similar across the 13 cohorts studied. These findings suggest that, although cohorts subjected to prolonged and extreme nutritional deprivation in utero and during infancy and early childhood suffer an immediate rise in mortality, after the crisis has passed, they carry no aftereffects that influence their survival in later life.

According to the foetal-origins hypothesis the risk of adult morbidity and mortality is heightened by intrauterine growth retardation. Twins, and in particular monozygotic twins, experience growth retardation in utero. A total of 8495 twin individuals born 1870-1900 in Denmark were followed through 1991 and death rates were calculated on a cohort basis. Deaths rates for twins and the general population were not significantly different except for females aged 60-89: mortality for female twins in this age group was 1.14 times (SE 0.03) higher than the general population. Female dizygotic twins experienced death rates 1.77 times (SE 0.18) higher than monozygotic twins at ages 30-59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age six. The findings in the present study suggest that the foetal-origins hypothesis is not true for the intrauterine growth retardation experienced by twins.

Objective: To test the validity of the fetal origins hypothesis and the classic twin method., Design: Follow up study of pairs of same sex twins in which both twins survived to age 6., Setting: Denmark., Subjects: 8495 twin individuals born 1870-1900, followed through to 31 December 1991., Main Outcome Measures: Mortality calculated on a cohort basis., Results: Mortality among twins and the general population was not significantly different except among females aged 60-89, in whom mortality among twins was 1.14 times (SE 0.03) higher than in the general population. Mortality among female dizygotic twins was 1.77 times (0.18) higher than among monozygotic twins at age 30-59. Otherwise, mortality for monozygotic and dizygotic twins did not consistently differ after age 6., Conclusion: According to the fetal origins hypothesis the risk of adult morbidity and mortality is heightened by retardation in intrauterine growth. Twins, and in particular monozygotic twins, experience growth retardation in utero. The findings in the present study suggest that the fetal origins hypothesis is not true for the retardation in intrauterine growth experienced by twins. Furthermore, the data are inconsistent with the underlying assumption of a recent claim that the classic twin method is invalid for studies of adult diseases. The present study is, however, based on the one third of all pairs of twins in which both twins survived to age 6. The possible impact of this selection can be evaluated in future studies of cohorts of younger twins with lower perinatal and infant mortality.

Study Question: Is fecundity, measured as self-reported time to first pregnancy (TTP), a marker for subsequent health and survival?Summary Answer: Long TTP was a marker for increased mortality among women and higher hospitalization rates for both women and men.What Is Known Already: Poor semen quality has been linked to increased mortality and morbidity from a wide range of diseases. Associations among fecundity, health and survival among women are still uncertain and studies on actual measures of fecundity and health outcomes are rare.Study Design, Size, Duration: We performed a prospective cohort study of 7825 women and 6279 men, aged 18 and above with measures on first TTP, who participated in one of the Danish nation-wide twin surveys in 1994 (twins born 1953-1976) and 1998 (twins born 1931-1952). They were followed-up for mortality and hospital admissions from the interview until 2018.Participants/materials, Setting, Methods: Twins were identified in the Danish Twin Registry and linked to Danish registers. TTP was restricted to the first pregnancy as a categorical outcome with cut-off points at 2, 10 and 18 months. We analysed the association between TTP and survival using a Cox proportional hazards model estimating hazards ratios (HRs) with 95% confidence intervals (CIs). Fine-Gray survival models were used to estimate sub-hazard ratios for specific causes of death allowing for competing risks. Using negative binomial regression, we estimated incidence rate ratios (IRRs) with 95% CIs for all-cause and cause-specific hospitalizations. All analyses were stratified by sex and adjusted for age at interview, birth cohorts, age at first attempt to become pregnant, smoking, years in school and BMI.Main Results and the Role Of Chance: In the total study population, 49.9% of women and 52.7% of men reported a TTP of less than 2 months, 30.8% of women and 29.6% of men reported a TTP of 2-9 months, 6.6% of women and 5.7% of men reported a TTP of 10-17 months, and 13.3% of women and 12.0% of men reported a TTP of 18 months or more. Among 1305 deaths, we found a higher mortality for women (HR = 1.46; 95% CI 1.15, 1.87) with a TTP of ≥18 months relative to those with a TTP of <2 months, while the highest mortality was indicated for men with a TTP of 10-17 months (HR = 1.31; 95% CI 0.98, 1.74). Among 53 799 hospitalizations, we found an increased hospitalization rate among women (HR = 1.21; 95% CI 1.0-1.41) and men (HR = 1.16; 95% CI 1.00-1.35) with a TTP of ≥18 months, and for men with a TTP of 2-9 months (HR = 1.14; 95% CI 1.01-1.30). A dose-response relationship was found for women regarding both mortality (P = 0.022) and hospitalizations (P = 0.018). Impaired fecundity was associated with a wide range of diseases and some causes of death, indicating a multi-factorial causal influence on fecundity, especially among women.Limitations, Reasons For Caution: A major limitation was that fecundity depends on both partners, which was not considered in this study. Moreover, we could not obtain information on a number of potential confounders.Wider Implications Of the Findings: Fecundity seems positively correlated with overall health and may be a universal marker of future health and survival. These results add knowledge to the limited findings showing that reduced fecundity in women and poor semen quality in men may reflect worse health and a shorter life, particularly among women.Study Funding/competing Interest(s): This study was funded by NIH grant HD096468 (M.L.E., T.K.J. and R.L.J.). The authors declare that they have no competing interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

OBJECTIVE To examine mortality and hospitalisations among infant twins and singletons after the perinatal period in Guinea-Bissau. METHODS The study was conducted from September 2009 to November 2012 by the Bandim Health Project (BHP). Newborn twins and unmatched singleton controls were included at the National Hospital Simão Mendes in the capital Bissau. Children were examined clinically at enrolment. Maternal, pregnancy and obstetric information was collected and HIV testing offered at birth. Follow-up occurred at home at 2, 6 and 12 months and through linkage with the paediatric admission register at the National Hospital. RESULTS About 495 twins and 333 singletons were alive on day 7 after birth. In total, 36 twins and 12 singletons died during follow-up, the post-perinatal infant mortality rate being 91/1000 personyears for twins and 42/1000 for singletons (HR = 2.11, 95% CI: 1.09-4.07). In a multivariable analysis among twins only, birth weight <2000 g [3.32, (1.36-8.07)], death of the cotwin perinatally [2.54, (1.16-5.57)] and severe maternal illness during pregnancy [2.35, (1.00-5.51)] were significant risk factors for twin death. In the subgroup with available HIV status, maternal HIV infection was strongly associated with twin mortality [3.16, (1.24-8.05)]. Death occurred at home for 60% of twins and 67% of singletons. During follow-up, 90 first-time hospital admissions were registered, with similar rates observed for twins (139/1000) and singletons (143/1000) [0.97, (0.61-1.52)]. CONCLUSION The post-perinatal infant mortality rate of twins was double that of singletons. No excess in twin hospitalisations was observed, possibly implying obstacles to hospital admission for twins in case of severe illness. [ABSTRACT FROM AUTHOR]

The antioxidant enzyme paraoxonase 1 (PON1) has previously been suggested to confer protection against coronary heart disease (CHD), one of the main causes of death in the Western world. Two coding polymorphisms, 55M/L and 192Q/R, and a promoter variant,-107C/T, has been extensively studied with respect to susceptibility to CHD. In this study, we have investigated the impact of these three polymorphisms on mortality using a sample of 1932 Danish individuals aged 47-93 years, previously used in gene-longevity studies. A cross-sectional study comparing the genotype distribution of the three polymorphisms separately as well as the haplotype distribution in different age groups did not reveal any difference. However, a longitudinal follow-up study on survival in the same sample indicated that 192RR homozygotes have a poorer survival compared to QQ homozygotes (hazard rate: 1.38, P=0.04). We hereafter used an independent sample of 541 Danish individuals from the oldest cohort and confirmed the initial findings (hazard rate: 1.38, P=0.09). In both samples, the effect was most pronounced in women. Using self-reported data on ischemic heart disease to evaluate the impact of the PON 192Q/R polymorphism on susceptibility to CHD, we found only a nonsignificant trend of 192RR homozygosity in women being a risk factor. Our results thus indicates that PON1 192RR homozygosity is associated with increased mortality in women in the second half of life and that this increased mortality is possibly related to CHD severity and survival after CHD rather than susceptibility to development of CHD.European Journal of Human Genetics (2004) 12, 843-847. doi:10.1038/sj.ejhg.5201235 Published online 7 July 2004 [ABSTRACT FROM AUTHOR]

Abstract: In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50–75years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7years the number of families with all participating siblings aged 95years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity. [Copyright &y& Elsevier]