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Fruit and Vegetable Intake and All-Cause Mortality in a Chinese Population: The China Health and Nutrition Survey. Gu Y, He Y, Ali SH, Harper K, Dong H, Gittelsohn J. Int J Environ Res Public Health. 2021 Jan 5;18(1):E342. doi: 10.3390/ijerph18010342. PMID: 33466375 Abstract This study was to investigate the association of long-term fruit and vegetable (FV) intake with all-cause mortality. We utilized data from the China Health and Nutrition Survey (CHNS), a prospective cohort study conducted in China. The sample population included 19,542 adult respondents with complete mortality data up to 31 December 2011. Cumulative FV intake was assessed by 3 day 24 h dietary recalls. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality. Covariates included sociodemographic characteristics, lifestyle factors, health-related factors, and urban index. A total of 1409 deaths were observed during follow-up (median: 14 years). In the fully adjusted model, vegetable intake of the fourth quintile (327~408 g/day) had the greatest negative association with death compared to the lowest quintile (HR = 0.63, 95% CI: 0.53-0.76). Fruit intake of the fifth quintile (more than 126 g/day) had the highest negative association (HR = 0.24, 95% CI: 0.15-0.40) and increasing general FV intake were also negatively associated with all-cause mortality which demonstrated the greatest negative association in the amount of fourth quintile (HR = 0.59, 95% CI: 0.49-0.70) compared to the lowest quintile. To conclude, greater FV intake is associated with a reduced risk of total mortality for Chinese adults. High intake of fruit has a stronger negative association with mortality than differences in intake of vegetables. Our findings support recommendations to increase the intake of FV to promote overall longevity. Keywords: China; fruit; mortality; prospective studies; vegetables. Leukocyte telomere length, cancer incidence and all-cause mortality among Chinese adults: Singapore Chinese Health Study. Samavat H, Luu HN, Beckman KB, Jin A, Wang R, Koh WP, Yuan JM. Int J Cancer. 2021 Jan 15;148(2):352-362. doi: 10.1002/ijc.33211. Epub 2020 Aug 5. PMID: 33459354 Abstract Telomeres play a key role in chromosomal maintenance and stability. To date, few studies have investigated the association of leukocyte telomere length with risk of cancer incidence and all-cause mortality in a large prospective cohort, particularly of the Asian population. Relative telomere lengths in genomic DNA from peripheral blood samples were quantified using a validated quantitative real-time PCR among 26 540 middle-aged or older Chinese adults. Hazard ratios (HRs) and 95% confidence intervals (CIs) of cancer and deaths by quintiles of telomere length were calculated using the Cox proportional hazards regression method with adjustment for age, sex and other potential confounders. After baseline blood collection, 4353 persons developed cancer and 7609 died. Participants with the longest decile of telomeres had a 26% (95% CI: 11%-44%) higher risk of total cancer incidence compared to the shortest decile after controlling for age, sex and other potential founders (Ptrend < .0001). In contrast, longer telomeres were associated with lower risk of all-cause mortality (HR = 0.93; 95% CI: 0.84-1.03), noncancer death (HR = 0.81; 95% CI: 0.71-0.92), specifically, death from chronic obstructive pulmonary disease and pneumonia (HR = 0.79, 95% CI: 0.70-0.89) and digestive diseases (HR = 0.60, 95% CI: 0.42-0.88). Our findings demonstrated that longer telomeres are associated with increased risk of cancer development overall and several common cancer types including breast, rectal, prostate, pancreatic cancer and lung adenocarcinoma. Our study also confirmed that longer telomeres are associated with a reduced risk of noncancer related death. Keywords: all‐cause mortality; biomarkers; cancer incidence; prospective cohort study; telomere length. Cognitive Trajectories and Resilience in Centenarians-Findings From the 100-Plus Study. Perls TT. JAMA Netw Open. 2021 Jan 4;4(1):e2032538. doi: 10.1001/jamanetworkopen.2020.32538. PMID: 33449091 No abstract available. [Free full-text from PMID abstract.] >>>>>>>>>>>>>>>>>>>> Association of Cognitive Function Trajectories in Centenarians With Postmortem Neuropathology, Physical Health, and Other Risk Factors for Cognitive Decline. Beker N, Ganz A, Hulsman M, Klausch T, Schmand BA, Scheltens P, Sikkes SAM, Holstege H. JAMA Netw Open. 2021 Jan 4;4(1):e2031654. doi: 10.1001/jamanetworkopen.2020.31654. PMID: 33449094 https://www.crsociety.org/search/?q=33449094 Abstract Importance: Understanding mechanisms associated with prolonged cognitive health in combination with exceptional longevity might lead to approaches to enable successful aging. Objective: To investigate trajectories of cognitive functioning in centenarians across domains, and to examine the association of these trajectories with factors underlying cognitive reserve, physical health, and postmortem levels of Alzheimer disease (AD)-associated neuropathology. Design, setting, and participants: This cohort study used neuropsychological test data and postmortem neuropathological reports from Dutch centenarians who were drawn from the 100-plus Study between January 2013 and April 2019. Eligible participants self-reported being cognitively healthy, which was confirmed by a proxy. Data analysis was performed between June 2019 and June 2020. Exposures: Age, sex, APOE ε genotype, factors of cognitive reserve, physical health, and AD-associated neuropathology (ie, amyloid-β, neurofibrillary tangles, and neuritic plaques). Main outcomes and measures: In annual visits (until death or until participation was no longer possible), centenarians underwent an extensive neuropsychological test battery, from which an mean z score of global cognition, memory, executive functions, verbal fluency, visuospatial functions, and attention/processing speed was calculated. Linear mixed models with a random intercept and time as independent variable were used to investigate cognitive trajectories, adjusted for sex, age, education, and vision and hearing capacities. In a second step, linear mixed models were used to associate cognitive trajectories with factors underlying cognitive reserve, physical health at baseline, and AD-associated neuropathology. Results: Of the 1023 centenarians approached, 340 were included in the study. We analyzed 330 centenarians for whom cognitive tests were available at baseline (239 [72.4%] women; median [interquartile range] age of 100.5 [100.2-101.7] years), with a mean (SD) follow-up duration of 1.6 (0.8) years. We observed no decline across investigated cognitive domains, with the exception of a slight decline in memory function (β, -0.10 SD per year; 95% CI, -0.14 to -0.05 SD; P < .001). Cognitive performance was associated with factors of physical health (eg, higher Barthel index: β, 0.37 SD per year; 95% CI, 0.24-0.49; P < .001) and cognitive reserve (eg, higher education: β, 0.41 SD per year; 95% CI, 0.29-0.53; P < .001), but none of these factors were associated with the rate of decline. Neuropathological reports were available for 44 participants. While centenarian brains revealed varying loads of postmortem neuropathological hallmarks of AD, this was not associated with cognitive performance or rate of decline. Conclusions and relevance: While we observed a slight vulnerability for decline in memory function, centenarians maintained high levels of performance in all other investigated cognitive domains for up to 4 years despite the presence of risk factors of cognitive decline. These findings suggest that mechanisms of resilience may underlie the prolongation of cognitive health until exceptional ages. NEWS AND VIEWS 14 JANUARY 2021 Anti-ageing effects of protein restriction unpacked Two animal studies show that restricting the dietary intake of branched-chain amino acids can extend lifespan by modulating the mTOR signalling pathway. But more research is needed before this diet should be recommended in people. https://www.nature.com/articles/d41586-020-03662-x >>>>>>>>>>>>>>>>> Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and life span in mice Nicole E. Richardson, Elizabeth N. Konon, Haley S. Schuster, Alexis T. Mitchell, Colin Boyle, Allison C. Rodgers, Megan Finke, Lexington R. Haider, Deyang Yu, Victoria Flores, Heidi H. Pak, Soha Ahmad, Sareyah Ahmed, Abigail Radcliff, Jessica Wu, Elizabeth M. Williams, Lovina Abdi, Dawn S. Sherman, Timothy A. Hacker & Dudley W. Lamming Nature Aging volume 1, pages73–86(2021) https://www.nature.com/articles/s43587-020-00006-2 Abstract Protein-restricted diets promote health and longevity in many species. While the precise components of a protein-restricted diet that mediate the beneficial effects to longevity have not been defined, we recently showed that many metabolic effects of protein restriction can be attributed to reduced dietary levels of the branched-chain amino acids (BCAAs) leucine, isoleucine and valine. Here, we demonstrate that restricting dietary BCAAs increases the survival of two different progeroid mouse models, delays frailty and promotes the metabolic health of wild-type C57BL/6J mice when started in midlife, and leads to a 30% increase in life span and a reduction in frailty in male, but not female, wild-type mice when they undergo lifelong feeding. Our results demonstrate that restricting dietary BCAAs can increase health span and longevity in mice and suggest that reducing dietary BCAAs may hold potential as a translatable intervention to promote healthy aging. An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila. Shi D, Han T, Chu X, Lu H, Yang X, Zi T, Zhao Y, Wang X, Liu Z, Ruan J, Liu X, Ning H, Wang M, Tian Z, Wei W, Sun Y, Li Y, Guo R, Wang Y, Ling F, Guan Y, Shen D, Niu Y, Li Y, Sun C. Cell Metab. 2021 Jan 7:S1550-4131(20)30672-0. doi: 10.1016/j.cmet.2020.12.017. Online ahead of print. PMID: 33440166 Abstract The health effect of dietary fat has been one of the most vexing issues in the field of nutrition. Few animal studies have examined the impact of high-fat diets on lifespan by controlling energy intake. In this study, we found that compared to a normal diet, an isocaloric moderately high-fat diet (IHF) significantly prolonged lifespan by decreasing the profiles of free fatty acids (FFAs) in serum and multiple tissues via downregulating FFA anabolism and upregulating catabolism pathways in rats and flies. Proteomics analysis in rats identified PPRC1 as a key protein that was significantly upregulated by nearly 2-fold by IHF, and among the FFAs, only palmitic acid (PA) was robustly and negatively associated with the expression of PPRC1. Using PPRC1 transgenic RNAi/overexpression flies and in vitro experiments, we demonstrated that IHF significantly reduced PA, which could upregulate PPRC1 through PPARG, resulting in improvements in oxidative stress and inflammation and prolonging the lifespan. Keywords: PPRC1; isocaloric moderately high-fat diet; lifespan; palmitic acid. Associations between daily aspirin use and cancer risk across strata of major cancer risk factors in two large U.S. cohorts. Hurwitz LM, Michels KA, Cook MB, Pfeiffer RM, Trabert B. Cancer Causes Control. 2020 Oct 26. doi: 10.1007/s10552-020-01357-2. Online ahead of print. PMID: 33104910 Abstract Purpose: Daily aspirin use has been shown to reduce risk of colorectal, and possibly other, cancers, but it is unknown if these benefits are consistent across subgroups of people with differing cancer risk factors. We investigated whether age, body mass index (BMI), smoking status, physical inactivity, and family history of cancer modify the effect of daily aspirin use on colorectal, ovarian, breast, endometrial and aggressive prostate cancer risk. Methods: We pooled 423,495 individuals from two prospective, U.S.-based studies: the NIH-AARP Diet and Health Study (1995-2011) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (1993-2009). Using Cox proportional hazards regression, we examined associations between daily aspirin use (≥ 5 days/week) and risk of colorectal, ovarian, breast, endometrial, and aggressive prostate cancer, overall and across strata of risk factors. Results: Daily aspirin use was associated with a 15% reduction in colorectal cancer risk (hazard ratio : 0.85, 95% confidence interval [CI] 0.80-0.89). Risk reductions were generally consistent across strata of risk factors but attenuated with increasing BMI (p-interaction = 0.16). For ovarian cancer, there was no significant association overall (HR: 0.93, 95% CI 0.80-1.08) but reduced risk among obese women (HR: 0.73, 95% CI 0.52-0.98, p-interaction = 0.12). Weak or null associations were observed for breast, endometrial, and aggressive prostate cancer, with no strong effect modification observed. Conclusions: Daily aspirin use appears to reduce colorectal cancer risk regardless of other risk factors, though the potential modifying effect of BMI warrants further investigation and may need to be considered in risk-benefit calculations for aspirin use. Keywords: Anti-inflammatory agents; Aspirin; Cancer risk; Chemoprevention; Effect modification; Non-steroidal. Physical activity and all-cause and cause-specific mortality: assessing the impact of reverse causation and measurement error in two large prospective cohorts. Lee DH, Rezende LFM, Ferrari G, Aune D, Keum N, Tabung FK, Giovannucci EL. Eur J Epidemiol. 2021 Jan 11. doi: 10.1007/s10654-020-00707-3. Online ahead of print. PMID: 33428024 Abstract Most cohort studies have only a single physical activity (PA) measure and are thus susceptible to reverse causation and measurement error. Few studies have examined the impact of these potential biases on the association between PA and mortality. A total of 133,819 participants from Nurses' Health Study and Health Professionals Follow-up Study (1986-2014) reported PA through biennial questionnaires. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for PA and mortality using different analytic approaches comparing single (baseline, simple update = most recent) versus repeated (cumulative average) measures of PA and applying various lag times separating PA measurement and time at risk. Over 3.2 million person-years, we documented 47,273 deaths. The pooled multivariable-adjusted HR (95% CI) of all-cause mortality per 10 MET-hour/week was 0.95 (0.94-0.96) for baseline PA, 0.78 (0.77-0.79) for simple updated PA and 0.87 (0.86-0.88) for cumulative average PA in the range of 0-50 MET-hour/week. Simple updated PA showed the strongest inverse association, suggesting larger impact of reverse causation. Application of 2-year lag substantially reduced the apparent reverse causation (0.85 (0.84-0.86) for simple updated PA and 0.90 (0.89-0.91) for cumulative average PA), and 4-12-year lags had minimal additional effects. In the dose-response analysis, baseline or simple updated PA showed a J or U-shaped association with all-cause mortality while cumulative average PA showed an inverse association across a wide range of PA (0-150 MET-hour/week). Similar findings were observed for different specific mortality causes. In conclusion, PA measured at baseline or with short lag time was prone to bias. Cumulative average PA showed robust evidence that PA is inversely associated with mortality in a dose-response manner. Keywords: Bias; Measurement error; Mortality; Physical activity; Reverse causation.