What to expect after a year in space: Space is the final frontier for understanding how extreme environments affect human physiology. Following twin astronauts, one of which spent a year-long mission on the International Space Station, Garrett-Bakelman et al. examined molecular and physiological traits that may be affected by time in space (see the Perspective by Löbrich and Jeggo). Sequencing the components of whole blood revealed that the length of telomeres, which is important to maintain in dividing cells and may be related to human aging, changed substantially during space flight and again upon return to Earth. Coupled with changes in DNA methylation in immune cells and cardiovascular and cognitive effects, this study provides a basis to assess the hazards of long-term space habitation. Science , this issue p. eaau8650 ; see also p. 127

Objective To examine whether adherence to the Mediterranean diet was associated with longer telomere length, a biomarker of aging. Design Population based cohort study. Setting Nurses’ Health Study, an ongoing prospective cohort study of 121 700 nurses enrolled in 1976; in 1989-90 a subset of 32 825 women provided blood samples. Participants 4676 disease-free women from nested case-control studies within the Nurses’ Health Study with telomere length measured who also completed food frequency questionnaires. Main outcome measure Association between relative telomere lengths in peripheral blood leukocytes measured by quantitative real time polymerase chain reaction and Alternate Mediterranean Diet score calculated from self reported dietary data. Results Greater adherence to the Mediterranean diet was associated with longer telomeres after adjustment for potential confounders. Least squares mean telomere length z scores were −0.038 (SE 0.035) for the lowest Mediterranean diet score groups and 0.072 (0.030) for the highest group (P for trend=0.004). Conclusion In this large study, greater adherence to the Mediterranean diet was associated with longer telomeres. These results further support the benefits of adherence to the Mediterranean diet for promoting health and longevity.

Newborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next generation has not been addressed. Average relative telomere lengths were measured in cord blood (n = 743) and placental tissue (n = 702) samples using a quantitative real-time PCR method from newborns from the ENVIRONAGE birth cohort in Belgium. By using univariate and multivariable adjusted linear regression models we addressed the associations between pre-pregnancy BMI and cord blood and placental telomere lengths. Maternal age was 29.1 years (range, 17–44) and mean (SD) pre-pregnancy BMI was 24.1 (4.1) kg/m2. Decline in newborn telomere length occurred in parallel with higher maternal pre-pregnancy BMI. Independent of maternal and paternal age at birth, maternal education, gestational age, newborn gender, ethnicity, birthweight, maternal smoking status, parity, cesarean section, and pregnancy complications, each kg/m2 increase in pre-pregnancy BMI was associated with a −0.50 % (95 % CI, −0.83 to −0.17 %; P = 0.003) shorter cord blood telomere length and a −0.66 % (95 % CI, −1.06 to −0.25 %; P = 0.002) shorter placental telomere length. Maternal pre-pregnancy BMI is associated with shorter newborn telomere lengths as reflected by cord blood and placental telomeres. These findings support the benefits of a pre-pregnancy healthy weight for promoting molecular longevity from early life onwards.

Accelerated telomere shortening has been associated with several age-related diseases and/or decreased lifespan in humans. The Mediterranean diet (MedDiet) is considered to be 1 of the most recognized diets for disease prevention and healthy aging, partially due to its demonstrated anti-inflammatory and antioxidative properties which may impact on telomere length (TL). The aim of this meta-analysis was to determine the associations between MedDiet adherence and TL maintenance. MEDLINE-PubMed and Cochrane databases were searched up to December 2018 for studies evaluating the association between MedDiet adherence and TL in blood cells. Two reviewers, working independently, screened all titles and abstracts to identify studies that met the inclusion criteria [cross-sectional, case-control, and prospective cohort studies and randomized clinical trials (RCTs) published in English and excluded nonoriginal articles]. Data were pooled by the generic inverse variance method using the random effects model and expressed as standardized mean difference (SMD). Heterogeneity was identified using the Cochran Q test and quantified by the I² statistic. A total of 8 original cross-sectional studies were included for the quantitative meta-analysis, comprising a total of 13,733 participants from 5 countries. A positive association between adherence to the MedDiet and TL was observed in all meta-analyses, with the exception of those conducted only in men: SMD (95% CI) of 0.130 (0.029; 0.231) for all subjects, 0.078 (0.005; 0.152) for women, and 0.095 (–0.005; 0.195) for men. Only 1 prospective cohort study and 1 RCT were identified, therefore, we could not undertake a meta-analysis for these study designs. The present meta-analysis of cross-sectional studies demonstrates that higher MedDiet adherence is associated with longer TL. At the same time, larger and high-quality prospective studies and clinical trials are warranted to confirm this association.

Endometrial cancer (EC) incidence is on the rise. Although early-onset endometrial cancer (EOEC; age at diagnosis <50 years) is relatively uncommon, the incidence of EOEC has been reportedly increasing in recent decades. However, the rising EOEC has not been thoroughly described with regard to the racial and ethnic disparities and compared with late-onset EC (age at diagnosis ≥50 years). We used the Cancer in North America (CiNA) Analytic File, 1995-2018, from the North American Association of Central Cancer Registries, which allowed us to examine trends in invasive EC incidence by racial and ethnic groups and by age at diagnosis. We found striking differences for demographic and tumor characteristics as well as racial and ethnic patterns and time trends in EC incidence between EOEC and late-onset EC. The faster increases in EOEC incidence rates, especially among non-White women, mirror similar observations in other cancers, pointing to a possible link with rising obesity epidemic in younger generations.

Introduction: PTPN22, PADI-4, and CTLA-4 have been associated with risk for rheumatoid arthritis (RA). We investigated whether polymorphisms in these genes were associated with RA in Caucasian women included in two large prospective cohorts, adjusting for confounding factors and testing for interactions with smoking. Methods: We studied RA risk associated with PTPN22 (rs2476601), PADI-4 (rs2240340), and CTLA-4 (rs3087243) in the Nurses' Health Study (NHS) and NHSII. Participants in NHS were aged 30 to 55 years at entry in 1976; those in NHSII were aged 25 to 42 years at entry in 1989. We confirmed incident RA cases through to 2002 in NHS and to 2003 in NHSII by questionnaire and medical record review. We excluded reports not confirmed as RA. In a nested case-control design involving participants for whom there were samples for genetic analyses (45% of NHS and 25% of NHSII), each incident RA case was matched to a participant without RA by year of birth, menopausal status, and postmenopausal hormone use. Genotyping was performed using Taqman single nucleotide polymorphism allelic discrimination on the ABI 7900 HT (Applied Biosystems, 850 Lincoln Centre Drive, Foster City, CA 94404 USA) with published primers. Human leukocyte antigen shared epitope (HLA-SE) genotyping was performed at high resolution. We employed conditional logistic regression analyses, adjusting for smoking and reproductive factors. We tested for additive and multiplicative interactions between each genotype and smoking. Results: A total of 437 incident RA cases were matched to healthy female control individuals. Mean (± standard deviation) age at RA diagnosis was 55 (± 10), 57% of RA cases were rheumatoid factor (RF) positive, and 31% had radiographic erosions at diagnosis. PTPN22 was associated with increased RA risk (pooled odds ratio in multivariable dominant model = 1.46, 95% confidence interval [CI] = 1.02 to 2.08). The risk was stronger for RF-positive than for RF-negative RA. A significant multiplicative interaction between PTPN22 and smoking for more than 10 pack-years was observed (P = 0.04). CTLA-4 and PADI-4 genotypes were not associated with RA risk in the pooled results (pooled odds ratios in multivariable dominant models: 1.27 [95% CI = 0.88 to 1.84] for CTLA-4 and 1.04 [95% CI = 0.77 to 1.40] for PADI-4). No gene-gene interaction was observed between PTPN22 and HLA-SE. Conclusion: After adjusting for smoking and reproductive factors, PTPN22 was associated with RA risk among Caucasian women in these cohorts. We found both additive and multiplicative interactions between PTPN22 and heavy cigarette smoking.