The role of the mitochondria in disease, general health and aging has drawn much attention over the years. Several attemptshave been made to describe how the numbersof mitochondriacorrelate with age, although with inconclusive results. In this study, the relativequantity of mitochondrial DNA compared to nuclear DNA,i.e. the mitochondrial DNA copy number, was measured by PCR technology and used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and singletons (18-93 years of age), with the majority being elderly individuals, theestimated mean mitochondrial DNA copy numberin peripheral blood cells was similar for those 18-48 years of age (mean relative mtDNA content: 61.0; 95% CI [52.1; 69.9]), but declinedby −0.54 mtDNA 95%CI [−0.63; −0.45] every year for those older thanapproximately 50 years of age.However, the longitudinal, yearly decline within an individual was more than twice as steep as observed in the cross-sectional analysis (decline of mtDNA content: −1.27; 95%CI [−1.71; −0.82]). Subjects with low mitochondrial DNA copy numberhad poorer outcomes in terms of cognitive performance, physical strength, self-rated health, andhigher all-cause mortality than subjects with high mitochondrial DNA copy number, also when age was controlled for.The copy numbermortality associationcan contribute to the smaller decline in a cross-sectional sample of the population compared to the individual,longitudinal decline. This study suggests that high mitochondrial DNA copy number in blood is associated with betterhealth and survival among elderly.

Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health.

BackgroundLeucocyte telomere length (LTL) is a complex trait associated with ageing and longevity. LTL dynamics are defined by LTL and its age-dependent attrition. Strong, but indirect evidence suggests that LTL at birth and its attrition during childhood largely explains interindividual LTL variation among adults. A number of studies have estimated the heritability of LTL, but none has assessed the heritability of age-dependent LTL attrition.MethodsWe examined the heritability of LTL dynamics based on a longitudinal evaluation (an average follow-up of 12 years) in 355 monozygotic and 297 dizygotic same-sex twins (aged 19–64 years at baseline).ResultsHeritability of LTL at baseline was estimated at 64% (95% CI 39% to 83%) with 22% (95% CI 6% to 49%) of shared environmental effects. Heritability of age-dependent LTL attrition rate was estimated at 28% (95% CI 16% to 44%). Individually unique environmental factors, estimated at 72% (95% CI 56% to 84%) affected LTL attrition rate with no indication of shared environmental effects.ConclusionsThis is the first study that estimated heritability of LTL and also its age-dependent attrition. As LTL attrition is much slower in adults than in children and given that having a long or a short LTL is largely determined before adulthood, our findings suggest that heritability and early life environment are the main determinants of LTL throughout the human life course. Thus, insights into factors that influence LTL at birth and its dynamics during childhood are crucial for understanding the role of telomere genetics in human ageing and longevity.

Twin pairs discordant for disease may help elucidate the epigenetic mechanisms and causal environmental factors in disease development and progression. To obtain the numbers of pairs, especially monozygotic (MZ) twin pairs, necessary for in-depth studies while also allowing for replication, twin studies worldwide need to pool their resources. The Discordant Twin (DISCOTWIN) consortium was established for this goal. Here, we describe the DISCOTWIN Consortium and present an analysis of type 2 diabetes (T2D) data in nearly 35,000 twin pairs. Seven twin cohorts from Europe (Denmark, Finland, Norway, the Netherlands, Spain, Sweden, and the United Kingdom) and one from Australia investigated the rate of discordance for T2D in same-sex twin pairs aged 45 years and older. Data were available for 34,166 same-sex twin pairs, of which 13,970 were MZ, with T2D diagnosis based on self-reported diagnosis and medication use, fasting glucose and insulin measures, or medical records. The prevalence of T2D ranged from 2.6% to 12.3% across the cohorts depending on age, body mass index (BMI), and national diabetes prevalence. T2D discordance rate was lower for MZ (5.1%, range 2.9-11.2%) than for same-sex dizygotic (DZ) (8.0%, range 4.9-13.5%) pairs. Across DISCOTWIN, 720 discordant MZ pairs were identified. Except for the oldest of the Danish cohorts (mean age 79), heritability estimates based on contingency tables were moderate to high (0.47-0.77). From a meta-analysis of all data, the heritability was estimated at 72% (95% confidence interval 61-78%). This study demonstrated high T2D prevalence and high heritability for T2D liability across twin cohorts. Therefore, the number of discordant MZ pairs for T2D is limited. By combining national resources, the DISCOTWIN Consortium maximizes the number of discordant MZ pairs needed for in-depth genotyping, multi-omics, and phenotyping studies, which may provide unique insights into the pathways linking genes to the development of many diseases.

OBJECTIVEVitamin D deficiency is thought to be a risk factor for development of type 2 diabetes, and elderly subjects at northern latitudes may therefore be at particular risk.RESEARCH DESIGN AND METHODSVitamin D status was assessed from serum concentrations of 25-hydroxyvitamin D3 [25(OH)D3] in 668 Faroese residents aged 70–74 years (64% of eligible population). We determined type 2 diabetes prevalence from past medical histories, fasting plasma concentrations of glucose, and/or glycosylated hemoglobin (HbA1c).RESULTSWe observed 70 (11%) new type 2 diabetic subjects, whereas 88 (13%) were previously diagnosed. Having vitamin D status <50 nmol/L doubled the risk of newly diagnosed type 2 diabetes after adjustment for BMI, sex, exposure to polychlorinated biphenyls, serum triacylglyceride concentration, serum HDL concentration, smoking status, and month of blood sampling. Furthermore, the HbA1c concentration decreased at higher serum 25(OH)D3 concentrations independent of covariates.CONCLUSIONSIn elderly subjects, vitamin D sufficiency may provide protection against type 2 diabetes. Because the study is cross-sectional, intervention studies are needed to elucidate whether vitamin D could be used to prevent development of type 2 diabetes.