Neighborhood Deprivation and Changes in Oral Health in Older Age: A Longitudinal Population-Based Study.

The aim of this study was to examine the extent to which neighborhood-level socioeconomic factors (objective and perceived) are associated with poor oral health in older adults over time, independent of individual socioeconomic position. Data for this cross-sectional and longitudinal observation study came from a socially and geographically representative cohort of men aged 71 to 92 y in 2010-12 (n = 1,622), drawn from British general practices, which was followed up in 2018-19 (aged 78-98 y; N = 667). Dental measures at both times included number of teeth, periodontal pocket depth, self-rated oral health, and dry mouth. Neighborhood deprivation was based on Index of Multiple Deprivation (IMD) and a cumulative index measuring perceptions about local environment. Individual-level socioeconomic position was based on longest-held occupation. Multilevel and multivariate logistic regressions, adjusted for relevant sociodemographic, behavioral, and health-related factors, were performed to examine the relationships of dental measures with IMD and perceived neighborhood quality index, respectively. Cross-sectionally, risks of tooth loss, periodontal pockets, and dry mouth increased from IMD quintiles 1 to 5 (least to most deprived); odds ratios (ORs) for quintile 5 were 2.22 (95% confidence interval [CI], 1.41-3.51), 2.82 (95% CI, 1.72-4.64), and 1.51 (95% CI, 1.08-2.09), respectively, after adjusting for sociodemographic, behavioral, and health-related factors. Risks of increased pocket depth and dry mouth were significantly greater in quintile 5 (highest problems) of perceived neighborhood quality index compared to quintile 1. Over the 8-y follow-up, deterioration of dentition (tooth loss) was significantly higher in the most deprived IMD quintiles after full adjustment (OR for quintile 5 = 2.32; 95% CI, 1.09-4.89). Deterioration of dentition and dry mouth were significantly greater in quintile 5 of perceived neighborhood quality index. Neighborhood-level factors were associated with poor oral health in older age, both cross-sectionally and longitudinally, particularly with tooth loss, and dry mouth, independent of individual-level socioeconomic position.

The Relationships of Dentition, Use of Dental Prothesis and Oral Health Problems with Frailty, Disability and Diet Quality: Results from Population-Based Studies of Older Adults from the UK and USA.

OBJECTIVES: This study examined the relationships of dental status, use and types of dental prothesis and oral health problems, individually and combined, with diet quality, frailty and disability in two population-based studies of older adults. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Men form the British Regional Heart Study (BRHS) (aged 85±4 years in 2018; n=1013) and Men and Women from the Health, Aging, and Body Composition (HABC) Study (aged 75±3 years in 1998-99; n=1975). MEASUREMENTS: Physical and dental examinations and questionnaires were collected with data available for dental status, oral problems related to eating, diet quality, Fried frailty phenotype, disability based on mobility limitations, and activities of daily living (ADL). The associations of dental status and oral health problems, individually and combined, with risk of frailty and disability were quantified. The relationship with diet quality was also assessed. RESULTS: In the BRHS, but not HABC Study, impaired natural dentition without the use of dentures was associated with frailty independently. This relationship was only established in the same group in those with oral problems (OR=3.24; 95% CI: 1.30-8.03). In the HABC Study, functional dentition with oral health problems was associated with greater risk of frailty (OR=2.21; 95% CI: 1.18-4.15). In both studies those who wore a full or partial denture in one or more jaw who reported oral problems were more likely to have disability. There was no association with diet quality in these groups. CONCLUSION: Older adults with impaired dentition even who use dentures who experience self-report oral problems related to eating may be at increased risk of frailty and disability. Further research is needed to establish whether improving oral problems could potentially reduce the occurrence of frailty and disability.

Translation of nutrigenomic research for personalised and precision nutrition for cancer prevention and for cancer survivors.

Personalised and precision nutrition uses information on individual characteristics and responses to nutrients, foods and dietary patterns to develop targeted nutritional advice that is more effective in improving the diet and health of each individual. Moving away from the conventional 'one size fits all', such targeted intervention approaches may pave the way to better population health, including lower burden of non-communicable diseases. To date, most personalised and precision nutrition approaches have been focussed on tackling obesity and cardiometabolic diseases with limited efforts directed to cancer prevention and for cancer survivors. Advances in understanding the biological basis of cancer and of the role played by diet in cancer prevention and in survival after cancer diagnosis, mean that it is timely to test and to apply such personalised and precision nutrition approaches in the cancer area. This endeavour can take advantage of the enhanced understanding of interactions between dietary factors, individual genotype and the gut microbiome that impact on risk of, and survival after, cancer diagnosis. Translation of these basic research into public health action should include real-time acquisition of nutrigenomic and related data and use of AI-based data integration methods in systems approaches that can be scaled up using mobile devices.

Design and baseline characteristics of the Biomarkers Of Risk In Colorectal Cancer (BORICC) Follow-Up study: A 12+ years follow-up.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Age is the strongest non-modifiable risk factor but it is estimated that over half of CRC cases are linked with lifestyle factors such as diet. The Biomarkers Of RIsk of Colorectal Cancer (BORICC) Study recruited 363 participants in 2005 to investigate the effects of lifestyle factors on biomarkers of CRC risk. AIM: In the present BORICC Follow-Up (BFU) Study, we are using a longitudinal study design to investigate the effects of ageing (12+ years) and lifestyle factors on biomarkers of CRC risk and on healthy ageing. METHODS: BFU Study participants attended a study visit at North Tyneside General Hospital (UK) for collection of biological samples, including blood and rectal biopsies, and information collected included anthropometric measurements, a Health & Medications Questionnaire, physical activity and sedentary behaviour, and habitual diet. Furthermore, musculoskeletal function was assessed by heel bone densitometry, timed up and go and hand grip strength as markers of healthy ageing. The BFU Study outcomes will be similar to those measured at baseline in the BORICC Study, such as DNA methylation and mitochondrial function, with additional measurements including the gut microbiome, faecal short-chain fatty acid concentrations and expression of genes associated with CRC. RESULTS: Participants' recruitment to BFU Study and all sample and data collection have been completed. Forty-seven of the original BORICC participants were re-recruited to the BFU Study (mean age 67 years, 51% female). The recruits included 37 initially healthy participants and 10 participants who had adenomatous polyps at baseline. Approximately 70% of participants were over-weight or obese. CONCLUSION: Ultimately, identifying lifestyle factors that can reduce CRC risk, and understanding the underlying mechanisms for the effects of lifestyle and ageing on CRC risk, could lead to early prevention strategies.

Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake.

INTRODUCTION: Dietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment. OBJECTIVES: To test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body. METHODS: We designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36). RESULTS: The experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables. CONCLUSION: It was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies.

Effects of obesity and weight loss on mitochondrial structure and function and implications for colorectal cancer risk.

Colorectal cancer (CRC) is the third most common cancer globally. CRC risk is increased by obesity, and by its lifestyle determinants notably physical inactivity and poor nutrition. Obesity results in increased inflammation and oxidative stress which cause genomic damage and contribute to mitochondrial dysregulation and CRC risk. The mitochondrial dysfunction associated with obesity includes abnormal mitochondrial size, morphology and reduced autophagy, mitochondrial biogenesis and expression of key mitochondrial regulators. Although there is strong evidence that increased adiposity increases CRC risk, evidence for the effects of intentional weight loss on CRC risk is much more limited. In model systems, energy depletion leads to enhanced mitochondrial integrity, capacity, function and biogenesis but the effects of obesity and weight loss on mitochondria in the human colon are not known. We are using weight loss following bariatric surgery to investigate the effects of altered adiposity on mitochondrial structure and function in human colonocytes. In summary, there is strong and consistent evidence in model systems and more limited evidence in human subjects that over-feeding and/or obesity result in mitochondrial dysfunction and that weight loss might mitigate or reverse some of these effects.

No effect of monthly supplementation with 12000 IU, 24000 IU or 48000 IU vitamin D3 for one year on muscle function: The vitamin D in older people study.

Vitamin D plays a role in muscle function through genomic and non-genomic processes. The objective of this RCT was to determine the effect of monthly supplemental vitamin D3 onmuscle function in 70+ years old adults. Participants (n = 379) were randomized to receive, 12,000 IU, 24,000 IU or 48,000 IU of vitamin D3 monthly for 12 months. Standardized Hand Grip Strength (GS) and Timed-Up and Go (TUG) were measured before and after vitamin D3 supplementation. Fasting total plasma 25 hydroxyvitamin D (25OHD) and Parathyroid Hormone (PTH) concentrations were measured by Liquid Chromatography Tandem Mass Spectrometry (LC-MSMS) and immunoassay, respectively. Baseline plasma 25OHD concentrations were 41.3 (SD 19.9), 39.5 (SD 20.6), 38.9 (SD 19.7) nmol/L; GS values were 28.5 (SD 13.4), 28.8 (SD 13.0) and 28.1 (SD 12.1) kg and TUG test values were 10.8 (SD 2.5), 11.6 (SD 2.9) and 11.9 (SD 3.6) s for the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. Baseline plasma 25OHD concentration < 25 nmol/L was associated with lower GS (P = 0.003). Post-interventional plasma 25OHD concentrations increased to 55.9 (SD 15.6), 64.6 (SD15.3) and 79.0 (SD 15.1) nmol/L in the 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively and there was a significant dose-related response in post-interventional plasma 25OHD concentration (p<0.0001). Post-interventional GS values were 24.1 (SD 10.1), 26.2 (SD10.6) and 25.7 (SD 9.4) kg and TUG test values were 11.5 (SD 2.6), 12.0 (SD 3.7) and 11.9 (SD 3.2) s for 12,000 IU, 24,000 IU and 48,000 IU dose groups, respectively. The change (Δ) in GS and TUG from pre to post-intervention was not different between treatment groups before and after the adjustment for confounders, suggesting no effect of the intervention. Plasma 25OHD concentration was not associated with GS and TUG test after supplementation. In conclusion, plasma 25OHD concentration < 25 nmol/L was associated with lower GS at baseline. However, monthly vitamin D3 supplementation with 12,000 IU, 24,000 IU and 48,000 IU, for 12 months had no effect on muscle function in older adults aged 70+ years. Trial Registration : EudraCT 2011-004890-10 and ISRCTN35648481.

Effects of vitamin C supplementation on glycaemic control: a systematic review and meta-analysis of randomised controlled trials.

Randomised controlled trials (RCTs) have observed contrasting results on the effects of vitamin C on circulating biomarkers of glycaemic and insulin regulation. We conducted a systematic review and meta-analysis of RCTs testing the effect of vitamin C administration on glucose, HbA1c and insulin concentrations. Four databases (PubMed, Embase, Scopus and Cochrane Library) were used to retrieve RCTs published from inception until April 2016 and testing the effects of vitamin C in adult participants. The screening of 2008 articles yielded 22 eligible studies (937 participants). Overall, vitamin C did not modify glucose, HbA1c and insulin concentrations. However, subgroup analyses showed that vitamin C significantly reduced glucose concentrations (-0.44 mmol/l, 95% CI: -0.81, -0.07, P=0.01) in patients with type 2 diabetes and in interventions with a duration greater than 30 days (-0.53%, 95% CI: -0.79, -0.10, P=0.02). Vitamin C administration had greater effects on fasting (-13.63 pmol/l, 95% CI: -22.73, -4.54, P<0.01) compared to postprandial insulin concentration. Meta-regression analyses showed that age was a modifier of the effect of vitamin C on insulin concentration. Furthermore, the effect size was associated with baseline BMI and plasma glucose levels, and with the duration of the intervention. In conclusion, greater reduction in glucose concentrations observed in patients with diabetes, older individuals and with more prolonged supplementation. Personalised interventions with vitamin C may represent a feasible future strategy to enhance benefits and efficacy of interventions. Nevertheless, results need to be interpreted cautiously due to limitations in the primary studies analysed.

Comparison of the portion size and frequency of consumption of 156 foods across seven European countries: insights from the Food4ME study.

There are no standardised serving/portion sizes defined for foods consumed in the European Union (EU). Typical serving sizes can deviate significantly from the 100 g/100 ml labelling specification required by the EU legislation. Where the nutritional value of a portion is specified, the portion size is determined by the manufacturers. Our objective was to investigate the potential for standardising portion sizes for specific foods, thereby ensuring complementarity across countries. We compared portion size for 156 food items measured using a food frequency questionnaire across the seven countries participating in the Food4me study. The probability of consuming a food and the frequency of consumption differed across countries for 93% and 58% of the foods, respectively. However, the individual country mean portion size differed from the average across countries in only 16% of comparisons. Thus, although dietary choices vary markedly across countries, there is much less variation in portion sizes. Our results highlight the potential for standardisation of portion sizes on nutrition labels in the EU.

Serum 25-hydroxyvitamin D concentration and its determinants in the very old: the Newcastle 85+ Study.

SUMMARY: Data on vitamin D status in very old adults are lacking. The aim of this study was to assess 25-hydroxyvitamin D [25(OH)D] concentrations and its predictors in 775 adults aged 85 years old living in North-East England. Low 25(OH)D was alarmingly high during winter/spring months, but its biological significance is unknown. INTRODUCTION: Despite recent concerns about the high prevalence of vitamin D deficiency in much of the British adult and paediatric population, there is a dearth of data on vitamin D status and its predictors in very old adults. The objective of the present study was to describe vitamin D status and its associated factors in a broadly representative sample of very old men and women aged 85 years living in the North East of England (55° N). METHODS: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] were analysed in 775 participants in the baseline phase of the Newcastle 85+ cohort study. Season of blood sampling, dietary, health, lifestyle and anthropometric data were collected and included as potential predictors of vitamin D status in ordinal regression models. RESULTS: Median serum 25(OH)D concentrations were 27, 45, 43 and 33 nmol/L during spring, summer, autumn and winter, respectively. The prevalence of vitamin D deficiency according to North American Institute of Medicine guidelines [serum 25(OH)D <30 nmol/L] varied significantly with season with the highest prevalence observed in spring (51%) and the lowest prevalence observed in autumn (23%; P < 0.001). Reported median (inter-quartile range) dietary intakes of vitamin D were very low at 2.9 (1.2-3.3) µg/day. In multivariate ordinal regression models, non-users of either prescribed or non-prescribed vitamin D preparations and winter and spring blood sampling were associated with lower 25(OH)D concentrations. Dietary vitamin D intake, disability score and disease count were not independently associated with vitamin D status in the cohort. CONCLUSION: There is an alarming high prevalence of vitamin D deficiency (<30 nmol/L) in 85-year-olds living in North East England at all times of the year but particularly during winter and spring. Use of vitamin D containing preparations (both supplements and medications) appeared to be the strongest predictor of 25(OH)D concentrations in these very old adults.

Ageing modifies the effects of beetroot juice supplementation on 24-hour blood pressure variability: An individual participant meta-analysis.

OBJECTIVES: Abnormal circadian oscillations of blood pressure (BP) and nocturnal-diurnal BP differences (i.e., dipping) increase cardiovascular risk. Whether inorganic nitrate supplementation influences 24-hr BP variability is currently unknown. We studied the effects of high-nitrate beetroot juice supplementation on BP variability measured by 24-hr ambulatory BP monitoring (24-hr ABPM) in older subjects. METHODS: Data from four independent randomised clinical trials were collated. Eighty-five older participants (age range: 55-76 years) were included in the final database. Two trials had an open-label, parallel design and two trials had a cross-over, double-blind design. Participants were randomised to either beetroot juice or placebo. Changes in 24-hr ABPM (daily, diurnal, nocturnal), variability (weighted-SDs), night-dipping, morning surge for systolic and diastolic BP were measured. Meta-analysis was conducted to obtain pooled estimates of the effect size for each BP outcome. Sub-group analyses were conducted to evaluate the influence of age, BMI, gender, BP status and changes in nitrite concentrations on the effect size. RESULTS: The pooled effect of beetroot juice on all BP outcomes was not significant. Beetroot juice ingestion determined a significant decrease in nocturnal systolic BP variability in subjects aged less than 65 y (2.8 mmHg, -4.5 -1.0, p = 0.002) compared to the older group (≥ 65 y; 1.0 mmHg, -2.2 4.2, p = 0.54). A greater change in NO2(-) concentrations after beetroot supplementation was associated with significant differences for nocturnal mean (-3.4 mmHg, -0.6 -2.4, p = 0.02) and variability (-0.8 mmHg, -1.5 -0.06, p = 0.03) of systolic BP. CONCLUSIONS: The vascular responsiveness to inorganic nitrate may be modified by mechanisms of vascular ageing influencing the reducing capacity to convert inorganic nitrate into nitrite and tissue-specific responses to dietary nitrate supplementation.

Associations between FTO genotype and total energy and macronutrient intake in adults: a systematic review and meta-analysis.

Risk variants of fat mass and obesity-associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrient intake has not been reviewed systematically. Our aim was to evaluate the potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in OVID MEDLINE, Scopus, EMBASE and Cochrane of associations between macronutrient intake and FTO genotype in adults. Beta coefficients and confidence intervals (CIs) were used for per allele comparisons. Random-effect models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213,173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal day(-1) (95% CI: 10.76, 2.16) lower total energy intake (P = 0.003). Total fat (P = 0.028) and protein (P = 0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P = 0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrient intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.

Instrumented assessment of test battery for physical capability using an accelerometer: a feasibility study.

Recent work has identified subdomains (tests) of physical capability that are recommended for assessment of the healthy ageing phenotype (HAP). These include: postural control, locomotion, endurance, repeated sit-to-stand-to-sit and TUG. Current assessment methods lack sensitivity and are error prone due to their lack of consistency and heterogeneity of reported outcomes; instrumentation with body worn monitors provides a method to address these potential weaknesses. This work proposes the use of a single tri-axial accelerometer-based device with appropriate algorithms (referred to here as a body worn monitor, BWM) for the purposes of instrumented testing during physicality capability assessment. In this pilot study we present 14 BWM-based outcomes across the subdomains which include magnitude, frequency and spatio-temporal characteristics. Where possible, we compared BWM outcomes with manually recorded values and found no significant differences between locomotion and TUG tasks (p ≥ 0.319). Significant differences were found for the total distance walked during endurance (p = 0.037) and times for repeated sit-to-stand-to-sit transitions (p < 0.000). We identified reasons for differences and make recommendations for future testing. We were also able to quantify additional characteristics of postural control and gait which could be sensitive outcomes for future HAP assessment. Our findings demonstrate the feasibility of this method to enhance measurement of physical capacity. The methodology can also be applied to a wide variety of accelerometer-based monitors and is applicable to a range of intervention-based studies or pathological assessment.

iCap: Instrumented assessment of physical capability.

OBJECTIVES: The aims of this study were to (i) investigate instrumented physical capability (iCap) as a valid method during a large study and (ii) determine whether iCap can provide important additional features of postural control and gait to categorise cohorts not previously possible with manual recordings. STUDY DESIGN: Cross-sectional analysis involving instrumented testing on 74 adults who were recruited as part of a pilot intervention study; LiveWell. Participants wore a single accelerometer-based monitor (lower back) during standardised physical capability tests so that outcomes could be compared directly with manual recordings (stopwatch and measurement tape) made concurrently. MAIN OUTCOME MEASURES: Time, distance, postural control and gait characteristics. RESULTS: Agreement between manual and iCap ranged from moderate to excellent (0.649-0.983) with mean differences between methods low and deemed acceptable. Additionally, iCap successfully quantified (i) postural control characteristics which showed sensitivity to distinguish between 5 variations of the standing balance test and (ii) 14 gait characteristics known to be sensitive to age/pathology. CONCLUSIONS: Our findings show that iCap can provide robust quantitative data about physical capability during standardised tests while also providing sensitive (age/pathology) postural control and gait characteristics not previously quantifiable with manual recordings. The methodology which we propose may have practical utility in a wide range of clinical and public health surveys and studies, including intervention studies, where assessment could be undertaken within diverse settings. This will need to be tested in further validation studies in a wider range of settings.

Instrumenting gait with an accelerometer: a system and algorithm examination.

Gait is an important clinical assessment tool since changes in gait may reflect changes in general health. Measurement of gait is a complex process which has been restricted to the laboratory until relatively recently. The application of an inexpensive body worn sensor with appropriate gait algorithms (BWM) is an attractive alternative and offers the potential to assess gait in any setting. In this study we investigated the use of a low-cost BWM, compared to laboratory reference using a robust testing protocol in both younger and older adults. We observed that the BWM is a valid tool for estimating total step count and mean spatio-temporal gait characteristics however agreement for variability and asymmetry results was poor. We conducted a detailed investigation to explain the poor agreement between systems and determined it was due to inherent differences between the systems rather than inability of the sensor to measure the gait characteristics. The results highlight caution in the choice of reference system for validation studies. The BWM used in this study has the potential to gather longitudinal (real-world) spatio-temporal gait data that could be readily used in large lifestyle-based intervention studies, but further refinement of the algorithm(s) is required.

Serum 25-hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study.

BACKGROUND AND PURPOSE: Studies investigating the association between 25-hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking. METHODS: Cross-sectional (baseline) and prospective data (up to 3 years follow-up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini-Mental State Examination) and attention-specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season-specific 25(OH)D quartiles. RESULTS: Those in the lowest and highest season-specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06-2.60, P = 0.03; 1.62, 95% confidence interval 1.02-2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log-transformed) attention reaction times for Choice Reaction Time (lowest, ß = 0.023, P = 0.01; highest, ß = 0.021, P = 0.02), Digit Vigilance Task (lowest, ß = 0.009, P = 0.05; highest, ß = 0.01, P = 0.02) and Power of Attention (lowest, ß = 0.017, P = 0.02; highest, ß = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, ß = 0.021, P = 0.02; highest, ß = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non-users of vitamin D supplements/medication. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention-specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.

25-hydroxyvitamin D and increased all-cause mortality in very old women: the Newcastle 85+ study.

OBJECTIVE: To investigate the associations between low and high concentrations of baseline serum 25-hydroxyvitamin D [25(OH)D] and all-cause mortality in very old (≥85 years) men and women over 6 years. DESIGN, SETTING AND SUBJECTS: Prospective mortality data from 775 participants in the Newcastle 85+ Study were analysed for survival in relation to 25(OH)D (season-specific quartiles and predefined cut-off values) and sex using Cox proportional hazards models. The models were fitted to the entire and restricted (nonusers of vitamin D-containing supplements and medication) cohorts. RESULTS: For the entire cohort, mortality was higher in both the lowest and highest 25(OH)D season-specific quartiles [SQ1: hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.01-1.69, P = 0.04; SQ4: HR 1.44, 95% CI 1.12-1.85, P = 0.004] compared with the combined middle quartiles (SQ2 + SQ3), after adjustment for sociodemographic factors. The increased risk for the highest quartile remained significant after further adjustment for lifestyle variables (SQ4: HR 1.37, 95% CI 1.06-1.77, P = 0.02) and was seen only in women in sex-specific analyses. Similarly, in sensitivity analyses with predefined 25(OH)D cut-off values, the highest 25(OH)D concentration (≥75 nmol L(-1) ) was associated with a 2.4-fold increased risk of mortality in women (restricted cohort) after adjusting for all covariates. CONCLUSION: Low and high season-specific 25(OH)D quartiles were associated with increased risks of mortality over 6 years in the very old; this effect was particularly noticeable in women, including those who reported taking vitamin D-containing supplements/medication.

Accuracy of three novel predictive methods for measurements of fat mass in healthy older subjects.

UNLABELLED: This study evaluated the agreement of novel anthropometric equations and established indirect methods (skinfold thickness and bioimpedance analysis) with reference methods [dual X-ray absorptiometry (DXA) and air displacement plethysmography (ADP)] for fat mass assessment (FM) in older subjects. METHODS: Forty subjects (M/F = 15/25, age = 61-84 years, BMI = 18-37 kg/m(2)) were recruited. The agreement of the following predictive equations was evaluated: body adiposity index (BAI), BAI-Fels and Clínica Universidad de Navarra-body adiposity estimator (CUN-BAE). RESULTS: BAI estimates were comparable to DXA (Δ ± 2SD = 0.4 ± 6.0 kg, p > 0.05) but not to ADP (Δ ± 2SD = -2.8 ± 7.2 kg, p < 0.001); BAI-Fels estimates were comparable to DXA (Δ ± 2SD = 0.8 ± 5.5 kg, p > 0.05) but not to ADP (Δ ± 2SD = -4.0 ± 6.9 kg, p < 0.001). The difference between CUN-BAE and ADP was not significant (Δ ± 2SD = -0.4 ± 5.6 kg, p > 0.05), whereas it significantly overestimated DXA (Δ ± 2SD = 2.8 ± 5.4 kg, p < 0.001). ADP significantly overestimated FM compared to DXA (Δ ± 2SD = 3.2 ± 5.4 kg, p < 0.001) and the measurement bias was significantly correlated with BMI in men (p = 0.004). CONCLUSIONS: The accuracy of the three anthropometric indexes is dependent on the choice of the reference method. The variability of the FM estimates was large and these indexes cannot be recommended for the assessment of FM in older subjects.

Early determinants of the ageing trajectory.

Over the past 250 years, human life expectancy has increased dramatically and continues to do so in most countries worldwide. Genetic factors account for about one third of variation in life expectancy so that most inter-individual variation in lifespan is explained by stochastic and environmental factors. The ageing process is plastic and is driven by the accumulation of molecular damage causing the changes in cell and tissue function which characterise the ageing phenotype. Early life exposures mark the developing embryo, foetus and child with potentially profound implications for the individual's ageing trajectory. Maternal factors including age, smoking, socioeconomic status, infections, nutritional status and season of birth influence offspring life expectancy and the development of age-related diseases. Although the mechanistic processes responsible are poorly understood, many of these factors appear to affect foetal growth directly or via effects on placental development. Those born relatively small i.e. which did not achieve their genetic potential in utero, appear to be at greatest disadvantage especially if they become overweight or obese in childhood. Early life events and exposures which enhance ageing are likely to contribute to molecular damage and/or reduce the repair of such damage. Such molecular damage may produce immediate defects in cellular or tissue function that are retained into later life. In addition, there is growing evidence that early life exposures produce aberrant patterns of epigenetic marks that are sustained across the life-course and result in down-regulation of cell defence mechanisms.

Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol.

AIMS/HYPOTHESIS: Type 2 diabetes is regarded as inevitably progressive, with irreversible beta cell failure. The hypothesis was tested that both beta cell failure and insulin resistance can be reversed by dietary restriction of energy intake. METHODS: Eleven people with type 2 diabetes (49.5 ± 2.5 years, BMI 33.6 ± 1.2 kg/m(2), nine male and two female) were studied before and after 1, 4 and 8 weeks of a 2.5 MJ (600 kcal)/day diet. Basal hepatic glucose output, hepatic and peripheral insulin sensitivity and beta cell function were measured. Pancreas and liver triacylglycerol content was measured using three-point Dixon magnetic resonance imaging. An age-, sex- and weight-matched group of eight non-diabetic participants was studied. RESULTS: After 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003). Insulin suppression of hepatic glucose output improved from 43 ± 4% to 74 ± 5% (p = 0.003 vs baseline; controls 68 ± 5%). Hepatic triacylglycerol content fell from 12.8 ± 2.4% in the diabetic group to 2.9 ± 0.2% by week 8 (p = 0.003). The first-phase insulin response increased during the study period (0.19 ± 0.02 to 0.46 ± 0.07 nmol min(-1) m(-2); p < 0.001) and approached control values (0.62 ± 0.15 nmol min(-1) m(-2); p = 0.42). Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min(-1) m(-2)). Pancreatic triacylglycerol decreased from 8.0 ± 1.6% to 6.2 ± 1.1% (p = 0.03). CONCLUSIONS/INTERPRETATION: Normalisation of both beta cell function and hepatic insulin sensitivity in type 2 diabetes was achieved by dietary energy restriction alone. This was associated with decreased pancreatic and liver triacylglycerol stores. The abnormalities underlying type 2 diabetes are reversible by reducing dietary energy intake.