Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10−11) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10−8). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10−8) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10−8) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

for the Depression Screening Data (DEPRESSD) PHQ Collaboration IMPORTANCE The Patient Health Questionnaire depression module (PHQ-9) is a 9-item self-administered instrument used for detecting depression and assessing severity of depression. The Patient Health Questionnaire-2 (PHQ-2) consists of the first 2 items of the PHQ-9 (which assess the frequency of depressed mood and anhedonia) and can be used as a first step to identify patients for evaluation with the full PHQ-9.OBJECTIVE To estimate PHQ-2 accuracy alone and combined with the PHQ-9 for detecting major depression.

Late-life loss of independence in daily living is a central concern for the aging individual and for society. The implications of increased survival to advanced age may be different at the population level than at the individual level. Here we used a longitudinal multiassessment survey of the entire Danish 1905 cohort from 1998 to 2005 to assess the loss of physical and cognitive independence in the age range of 92 to 100 years. Multiple functional outcomes were studied, including independence, which was defined as being able to perform basic activities of daily living without assistance from other persons and having a MiniMental State Examination (MMSE) score of 23 or higher. In the aggregate, the 1905 cohort had only a modest decline in the proportion of independent individuals at the 4 assessments between age 92 and 100 years: 39%, 36%, 32%, and 33%, with a difference between first and last assessment of 6% [95% confidence interval (CI), ؊1-14%]. For participants who survived until 2005, however, the prevalence of independence was reduced by more than a factor of 2, from 70% in 1998 to 33% in 2005 (difference, 37%; 95% CI, 28 -46%). Similar results were obtained for the other functional outcomes. Analyses of missing data resulting from nonresponse and death suggest that the discrepancy between the population trajectory and the individual trajectory is caused by increased mortality among dependent individuals. For the individual, long life brings an increasing risk of loss of independence. For society, mortality reductions are not expected to result in exceptional levels of disability in cohorts of the very old.centenarians ͉ nonagenarians ͉ survival ͉ independence T he oldest-old is the fastest growing segment of the population in the Western world, and the increase results mainly from a reduction in mortality rates among the oldest-old (1). There has been a longstanding debate within gerontology as to whether longer life is associated with a ''compression of morbidity'' (2), an ''expansion of morbidity'' (3, 4), or a combination of both, with an increased prevalence of chronic diseases counterbalanced by a decrease in the severity and consequences of the same diseases (5). The evidence supporting these different perspectives is mixed, perhaps because of differences in research settings (e.g., cohorts, countries, and ethnicities) and methodology (e.g., response rates and assessment instruments) (6-8). Nonetheless, there are accumulating data that the prevalence of chronic disability is decreasing among the elderly (6, 9). Although there is evidence that successive cohorts are living not only longer but also better (10-13), there still is considerable concern, both at the individual and societal level, that an extension of life into the highest ages in any birth cohort of elderly, now or in the future, will be accompanied by very high rates of loss of independence, with great personal and societal costs. Cross-sectional data indicate that dependency is considerably more prevalent in the oldest-old than in the ...

Grip strength (GS) has an age-and genderdependent decline with advancing age. One study comparing GS among extremely old show a North-South gradient with lowest GS in Italy compared to France (intermediary) and Denmark (highest) even after adjusting for confounders. As GS is associated with higher rates of functional decline and mortality, and thus may be used as a health indicator, it is of interest to examine whether the results on extremely old can be reproduced in a large-scale European survey. GS was measured in a cross-sectional population-based sample of 27,456 individuals aged 50? in 11 European countries included in the SHARE survey. We made a cross-country comparison of the age trajectory of GS in both genders. Northern-continental European countries had higher GS than southern European countries even when stratifying by age and gender and controlling for height, weight, education, health and socioeconomic status. The relative excess was found to be 11% and the absolute difference 5.0 kg for 50-to 54-year-old men, increasing to 28% and 6.9 kg among 80? year-old men. The corresponding figures for women were 16% and 4.3 kg, and 21% and 3.5 kg, respectively. Southern European countries have lower GS in the age range 50? year. Gene-environment interactions may explain country-specific differences. The use of GS in cross-national surveys should control not only for age and gender, but also for nationality.

The etiology of type 2 diabetes is multifactorial, including genetic as well as pre-and postnatal factors that influence several different defects of glucose homeostasis, primarily in muscle, ␤-cells, and liver. In the present twin study, we report heritability estimates (h 2 ) for measures of insulin secretion, insulin resistance, hepatic glucose production (HGP), and intracellular glucose partitioning using gold standard methods (euglycemic-hyperinsulinemic clamp technique, tritiated glucose infusion, indirect calorimetry, and intravenous glucose tolerance testing) among 110 younger