Plasma metabolomic profiles associated with mortality and longevity in a prospective analysis of 13,512 individuals.

Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined.

Intake of fruits and vegetables by pesticide residue status in relation to cancer risk.

BACKGROUND: Conventionally grown fruits and vegetables (FVs) are the main source of general population exposure to pesticide residues. OBJECTIVE: To evaluate the relation of intake of high- and low-pesticide-residue FVs with cancer risk. METHODS: We followed 150,830 women (Nurses' Health Study, 1998-2016, and Nurses' Health Study II, 1999-2017) and 29,486 men (Health Professionals Follow-up Study, 1998-2016) without a history of cancer. We ascertained FV intake via validated food frequency questionnaires and categorized FVs as having high or low pesticide residue levels based on USDA surveillance data. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total and site-specific cancer related to quintiles of high- and low-pesticide-residue FV intake. RESULTS: We documented 23,678 incident cancer cases during 2,862,118 person-years of follow-up. In the pooled multivariable analysis, neither high- nor low-pesticide-residue FV intake was associated with cancer. The HRs (95% CI) per 1 serving/day increase in intake were 0.99 (0.97-1.01) for high- and 1.01 (0.99-1.02) for low-pesticide-residue FVs. Additionally, we found no association between high-pesticide-residue FV intake and risk of specific sites, including malignancies previously linked to occupational pesticide exposure ([HR, 95% CI comparing extreme quintiles of intake] lung [1.17 (0.95-1.43)], non-Hodgkin lymphoma [0.89 (0.72-1.09)], prostate [1.31 (0.88-1.93)]) or inversely related to intake of organic foods (breasts [1.03 (0.94-1.31)]). CONCLUSIONS: These findings suggest that overall exposure to pesticides through FV intake is not related to cancer risk, although they do not rule out associations with specific chemicals or sub-types of specific cancers.

Night Shift Work Before and During Pregnancy and Offspring Weight Outcomes Through Adolescence.

OBJECTIVE: This study aimed to investigate associations between maternal history of rotating night shift nursing work before pregnancy and number of night shifts worked during pregnancy with offspring weight outcomes from early life through adolescence. METHODS: More than 4,000 children, enrolled in the second phase of the Growing Up Today Study between 2004 and 2013, and their mothers participating in the Nurses' Health Study II were included in our analyses. RESULTS: Children of women with and without a history of rotating night shift work before pregnancy were similar in birth weight and body size at age 5. However, for mothers with night shift work before pregnancy, their children had a modestly elevated risk of having overweight or obesity (relative risk = 1.11; 95% CI: 1.02-1.21), which was stronger for persistently having overweight or obesity during adolescence and early adulthood. Longer duration of rotating night shift work was not associated with any of these weight outcomes. Weight outcomes of children of women with versus without night shift work during pregnancy were similar, regardless of frequency of night shifts worked during pregnancy (all P > 0.09). CONCLUSIONS: Overall, nurses' night shift work before or during pregnancy did not affect offspring weight outcomes. Future larger studies should explore these associations in more detail.

Phobic anxiety and plasma levels of global oxidative stress in women

Background and Objectives: Psychological distress has been hypothesized to be associated with adverse biologic states such as higher oxidative stress and inflammation. Yet, little is known about associations between a common form of distress -phobic anxiety- and global oxidative stress. Thus, we related phobic anxiety to plasma fluorescent oxidation products (FlOPs), a global oxidative stress marker. Methods: We conducted a cross-sectional analysis among 1,325 women (aged 43-70 years) from the Nurses' Health Study. Phobic anxiety was measured using the Crown-Crisp Index (CCI). Adjusted least-squares mean log-transformed FlOPs were calculated across phobic categories. Logistic regression models were used to calculate odds ratios (OR) comparing the highest CCI category (≥ 6 points) vs. lower scores, across FlOPs quartiles. Results: No association was found between phobic anxiety categories and mean FlOP levels in multivariable adjusted linear models. Similarly, in multivariable logistic regression models there were no associations between FlOPs quartiles and likelihood of being in the highest phobic category. Comparing women in the highest vs. lowest FlOPs quartiles: FlOP_360: OR = 0.68 (95% CI: 0.40 - 1.15); FlOP_320: OR = 0.99 (95% CI: 0.61 - 1.61); FlOP_400: OR = 0.92 (95% CI: 0.52, 1.63). Conclusions: No cross-sectional association was found between phobic anxiety and a plasma measure of global oxidative stress in this sample of middle-aged and older women

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