BACKGROUND AND AIMS: The level of physical functioning (PF) late in life has, in recent years, been shown to be influenced by genetic factors. One of the most extensively studied genetic variants associated with PF and trainability is insertion/deletion (I/D) polymorphism in the gene encoding Angiotensin Converting Enzyme (ACE). However, ACE studies have mainly been conducted among younger persons in excellent physical shape. In this study, we examine whether the level of PF, trainability, or rate-of-change are associated with the ACE genotype among the elderly. METHODS: We used data from 4 randomized training studies of elderly Danes (N = 203). The measures of PF were self-report, maximal oxygen uptake, muscle strength, walking speed, and body composition. RESULTS: Overall, a favorable change in the measures of PF was observed in training groups compared with control groups. However, within groups, neither pre- or post-training/control period levels of PF nor differences in pre- and post-levels were associated with the ACE genotype. CONCLUSIONS: On the basis of our randomized studies, we could not detect any association between the ACE genotype and the level of PF or change, regardless of whether response to physical training or spontaneous changes was studied.
Genetic-evolutionary theories of aging predict that the genetic variance for fitness traits increases with age, while epidemiological-gerontological theories predict an increase in the environmental variance for most traits. In this study we examine the age trajectories of the genetic and environmental variance in physical functioning in a sample of 4731 Danish twins aged 70+ who are being followed longitudinally every second year with up to four assessments completed. A biometric growth model (Neale and McArdle, 2000) was applied to a validated physical ability score. The model included an overall level effect, a rate of linear change effect, and residual effects. The best-fitting model was a sex-specific model including additive genetic and nonshared environmental factors affecting level and rate of change and only nonshared environmental factors affecting the wave-specific levels. For both sexes there is an approximate doubling of both the total variance and the genetic variance in the physical ability score over the four waves and, hence, a rather stable heritability. However, the heritability is approximately.10 for males and.30 for females in all four waves. The heritability of level and slope showed a similar pattern:.11-14 in males and.35-.39 in females. The increase in both additive genetic variance and environmental variance is in agreement with genetic-evolutionary and epidemiological-gerontological theories of aging, respectively. The present study suggests that overall level of strength may be a better phenotype for future molecular genetic studies on physical functioning in the elderly than rate of change, because rate of change is vulnerable to sample attrition due to mortality and dropout and because four waves were needed to be able to detect a heritability for rate of change of the same magnitude as the heritability for level of physical functioning.
We have studied the possible association between the -110A > C polymorphism in the promoter region of one of the heat shock protein genes HSP70-1 with human longevity in a cohort of aged Danish twins. This cohort includes individuals aged between 70 and 91 years (mean = 75.6 years), who are categorized according to the presence or absence of various diseases and according to the various, age-related parameters for which a genetic component has already been defined. Four hundred DNA samples from the cohort were genotyped using real-time PCR. Aging phenotypes (diseases, physical and cognitive functioning) were compared with regard to genotype. Of all the aging phenotypes studied, self-rated health and relative self-rated health, which represent an individual's overall sense of physical well-being and which have been shown to be both predictors of survival at older ages and better indicators of future survival than objectively measured health status, were associated with the polymorphism. An association was found between low self-rated health and heterozygosity for -110A > C polymorphism in the promoter region of HSP70-1 in aged Danish twins.
STUDY DESIGN: Cross-sectional and longitudinal analysis of data comprising 4486 Danish twins 70-102 years of age. OBJECTIVES: To describe the 1-month prevalence of back pain, neck pain, and concurrent back and neck pain and the development of these over time, associations with other health problems, education, smoking, and physical, and mental functioning. SUMMARY OF BACKGROUND DATA: Back pain and neck pain are prevalent symptoms in the population; however, there is little research addressing these conditions in older age groups. METHODS: Extensive interview data on health, lifestyle, social, and educational factors were collected in a nationwide cohort-sequential study of 70+-year-old Danish twins. Data for back pain, neck pain, lifetime prevalence of a comprehensive list of diseases, education, and self-rated health were based on self-report. Physical and mental functioning were measured using validated performance tests. Data including associated factors were analyzed in a cross-sectional analysis for answers given at entry into the study, and longitudinal analysis was performed for participants in all four surveys. RESULTS: The overall 1-month prevalence for back pain only was 15%, for neck pain only 11%, and for concurrent back and neck pain 11%. The prevalence varied negligibly over time and between the age groups, and 63% of participants in all surveys had no episodes or only one episode of back or neck pain. Back pain and neck pain were associated with a number of other diseases and with poorer self-rated health. Back and neck pain sufferers had significantly lower scores on physical but not cognitive functioning. CONCLUSIONS: Back pain and neck pain are common, intermittent symptoms in old age. Back pain and neck pain are associated with general poor physical health in old age.
Back pain (BP) has been rated among the most important factors affecting physical health status in old age. Yet there is an under-representation of the older population in the BP literature. We present extensive interview data from the Longitudinal Study of Aging Danish Twins, dealing with a population-based sample of Danish twins aged 70-102, and describing the 1-month prevalence of BP and the development of BP over time. The associations between BP and education, self-rated health, other health problems, lifestyle factors, and physical and mental function were also investigated. Data were analysed in a cross-sectional analysis for all answers given at entry into the study and in a longitudinal analysis for participants in all four surveys. Associated factors were analysed for the cross-sectional sample using univariate and multivariate analysis accounting for the non-independence of twins in complete pairs. The overall 1-month prevalence of BP was 25% and differed significantly between men and women. The variations in prevalence between the age groups and over time were negligible. The majority of participants in all four surveys had either not experienced BP during the previous month or had done so on one occasion only. Education was not associated with BP. Self-rated health was associated with BP in a significant "dose-response" like pattern. BP was associated with bone and joint disorders, migraine headaches, lung disease, cardiovascular disorders and gastric ulcer, but not neurologic or endocrinologic diseases. BP sufferers had significantly lower scores on physical but not on mental functioning. We conclude that BP is a common symptom in old age; however, the prevalence does not change with increasing age. BP may be part of a more general syndrome of poor health among the old.
Patients with systemic mastocytosis have an increased risk of osteoporosis, however, the risk of osteoporotic fractures among the classic chronic myeloproliferative neoplasms (CMPN), including essential thrombocythaemia (ET), polycythaemia vera (PV) and chronic myeloid leukaemia (CML), is unknown. We conducted a population-based cohort study to determine the risk of osteoporotic fractures among three cohorts of patients with newly diagnosed ET, PV, and CML. Patients were identified in medical registers including all Danish hospitals during 1980-2010 and were followed until first osteoporotic fracture. Fracture risk was compared to cohorts from the general population matched on age, sex and calendar year. We followed 7595 CMPN patients and 338 974 comparison cohort members. We found that the risk of femoral fracture after 5 years was consistently higher than the general population, being 3·01% (95% confidence interval (CI): 2·20-4·10), 4·74% (95%CI: 4·06-5·52) and 4·64% (95%CI: 3·29-6·53) among ET, PV, and CML patients respectively. Adjusted hazard ratio for femoral fracture was increased 1·19-fold (95% CI: 0·94-1·51) for ET patients, 1·82-fold (95% CI: 1·62-2·04) for PV patients, and 2·67-fold (95% CI: 1·97-3·62) for CML patients. We conclude that CMPN patients are at higher risk of osteoporotic fractures than the general population.
Patients with chronic myeloproliferative neoplasms, including essential thrombocythemia (ET), polycythemia vera (PV), and chronic myeloid leukemia (CML), are at increased risk of new hematologic malignancies, but their risk of nonhematologic malignancies remains unknown. In the present study, we assessed the risk of both types of malignancies after an ET, PV, or CML diagnosis. We linked 2 population-based nationwide registries, the Danish National Registry of Patients, covering all Danish hospitals and the Danish Cancer Registry, and assessed subsequent cancer risk in a cohort of all 7229 patients diagnosed with a chronic myeloproliferative neoplasm during 1977-2008. We compared the incidence of subsequent cancer in this cohort with that expected on the basis of cancer incidence in the general population (standardized incidence ratio). Overall, ET, PV, and CML patients were at increased risk of developing both new hematologic and nonhematologic cancers. The standardized incidence ratio for developing a nonhematologic cancer was 1.2 (95% confidence interval [95% CI]): 1.0-1.4) for patients with ET, 1.4 (95% CI: 1.3-1.5) for patients with PV, and 1.6 (95% CI: 1.3-2.0) for patients with CML. We conclude that patients with chronic myeloproliferative neoplasms are at increased risk of developing a new malignant disease.
BACKGROUND: Long-lived individuals are rare and may be selected in part for the genetic factors that promote successful aging. The children of long-lived parents may therefore age more successfully than the children of short-lived parents. METHODS: We used three major cross-sectional population-based surveys to study the association of parental longevity with successful aging in offspring. The measures of aging were hand-grip strength, cognitive performance (Mini Mental State Examination and a cognitive composite score), self-reported diseases, and self-rated health. RESULTS: For every additional 10 years the parents lived, their children's grip strength increased by 0.32 kg (95% CI = 0.00-0.63), Mini Mental State Examination score by 0.20 points (95% CI = 0.03-0.37), and cognitive composite score by 0.24 points (95% CI = 0.07-0.40). A 10-year increment of parental life was associated with a reduction by approximately 0.20 in the adjusted odds ratio for their children having each of the following conditions: diabetes; hypertension; ischemic heart disease; heart failure; stroke; or fair, poor, or very poor self-rated health. Almost all the effects were seen solely in the cohort of 70+-year-olds, but not among middle-aged or nonagenarian subjects. CONCLUSIONS: Parental life span is positively associated with the children's physical and cognitive functioning and avoidance of some of the common chronic diseases. However, the effects are small and are seen among offspring who are elderly, but not among the middle-aged or the oldest old.
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.
Erratum In: Spine. 2005 Mar 15;30(6):710Pedersen, Hans Christian [corrected to Petersen, Hans Christian]
The microarray technique is an important tool in gene expression analysis to study the activities of thousands of genes measured by their transcript levels under disease or laboratory controlled experimental conditions. Recent studies have suggested a genetic component in the variations of gene expression thus indicating the important role of genetic control over gene activities. In this study, we analyze and report the twin correlation on gene expression in whole blood samples of six female Danish twin pairs aged from 81 to 85 years. We studied the expression phenotype by treating the measured gene expression as a quantitative trait and introducing analytical approaches including the traditional twin methods in population genetics and the multivariate statistical methods. Using this combinatory approach, we were able to estimate and compare the twin correlation on the expression phenotype while accounting for systematic influence in microarray experiments. Analyses on our twin data detected a significant correlation on the expression levels of the actively regulated genes in both monozygotic and dizygotic twins, which is more pronounced in monozygotic twins. Gene ontology analysis has shown that these actively regulated genes are predominantly involved in defense and immune responses against antigenic stimulus. In conclusion, the correlation patterns revealed in our twin data provide evidence of the existence of a heritable mechanism in gene expression regulation persistently functioning even in aged subjects.