RISK OF CARDIOVASCULAR DISEASE MORBIDITY AND MORTALITY IN FRAIL AND PRE-FRAIL OLDER ADULTS:RESULTS FROM A META-ANALYSIS AND EXPLORATORY META-REGRESSION ANALYSIS

Frailty is common and associated with poorer outcomes in the elderly, but its role as potential cardiovascular disease (CVD) risk factor requires clarification. We thus aimed to meta-analytically evaluate the evidence of frailty and pre-frailty as risk factors for CVD. Two reviewers selected all studies comparing data about CVD prevalence or incidence rates between frail/pre-frail vs. robust. The association between frailty status and CVD in cross-sectional studies was explored by calculating and pooling crude and adjusted odds ratios (ORs)+/- 95% confidence intervals (CIs); the data from longitudinal studies were pooled using the adjusted hazard ratios (HRs). Eighteen cohorts with a total …

Interventions to Slow Aging in Humans: Are We Ready?

The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consens…

A Comparison of Objective Physical Performance Tests and Future Mortality in the Elderly People.

Background: Physical performance is an important predictor of mortality, but little is known on the comparative prognostic utility of different objective physical performance tests in community-dwelling older adults. We compared the prognostic usefulness of several objective physical performance tests on mortality, adjusting our analyses for potential confounders. Methods: Among 3,099 older community-dwelling participants included in the Progetto Veneto Anziani study, 2,096 were followed for a mean of 4.4 years. Physical performance tests measured were Short Physical Performance Battery (SPPB), 4-meter gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute…

Reply to KA Beals and to C Parks

Fried potato consumption is associated with elevated mortality: an 8-y longitudinal cohort study

Background: Few studies have assessed the association between potato consumption and mortality. Objective: We investigated whether potato consumption (including fried and unfried potatoes) is associated with increased premature mortality risk in a North American cohort. Design: A longitudinal analysis included 4440 participants aged 45-79 y at baseline with an 8-y follow-up from the Osteoarthritis Initiative cohort study. Potato consumption (including fried and unfried potatoes) was analyzed by using a Block Brief 2000 food-frequency questionnaire and categorized as ≤1 time/mo, 2-3 times/mo, 1 time/wk, 2 times/wk, or ≥3 times/wk. Mortality was ascertained through validated cases of death. T…

Dietary fiber and health outcomes: an umbrella review of systematic reviews and meta-analyses

Background Several studies have suggested that higher consumption of dietary fiber is beneficial for a variety of health outcomes. However, many results have been inconclusive and, to our knowledge, there has been no attempt to systematically capture the breadth of outcomes associated with dietary fiber intake or to systematically assess the quality and the strength of the evidence on the associations of dietary fiber intake and different health outcomes or medical conditions. Objective The aim of this study was to describe the diverse health outcomes convincingly associated with dietary fiber consumption. Design This was an umbrella review of systematic reviews with meta-analysis of observ…

Frailty Is Associated with an Increased Risk of Incident Type 2 Diabetes in the Elderly

Objective To investigate whether frailty is associated with an increased risk of incident type 2 diabetes mellitus (T2DM) in a prospective cohort of community-dwelling older people. Design Longitudinal study, mean follow-up of 4.4 years. Setting Progetto Veneto Anziani (Pro.V.A.) study that involved older community-dwellers. Participants 1754 men and women older than 65 years without T2DM at baseline. Measurements Frailty status was defined according to Fried criteria and categorized as frailty (≥3 criteria), prefrailty (1-2 criteria), or no frailty (0 criterion). Incident T2DM was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, or glycosylated hemoglobin ≥6.5%, the use of glucose-lowe…

Decreased consumption of branched-chain amino acids improves metabolic health

Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino…

Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle

Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to…

Impact of intermittent energy restriction on anthropometric outcomes and intermediate disease markers in patients with overweight and obesity: systematic review and meta-analyses

This systematic review aims to investigate the effects of intermittent energy restriction (IER) on anthropometric outcomes and intermediate disease markers. A systematic literature search was conducted in three electronic databases. Randomized controlled trials (RCTs) were included if the intervention lasted ≥12 weeks and IER was compared with either continuous energy restriction (CER) or a usual diet. Random-effects meta-analysis was performed for eight outcomes. Certainty of evidence was assessed using GRADE. Seventeen RCTs with 1328 participants were included. IER in comparison to a usual diet may reduce body weight (mean difference [MD]: −4.83 kg, 95%-CI: −5.46, −4.21; n = 6 RCTs), wais…

Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population

SummaryMice and humans with growth hormone receptor/IGF-1 deficiencies display major reductions in age-related diseases. Because protein restriction reduces GHR-IGF-1 activity, we examined links between protein intake and mortality. Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived. Conversely, high protein intake was associated with reduced cancer and overall mortality in respondents over 65, but a 5-fold increase in diabetes mortality across all ages. Mouse studies confirmed the effect…

Associations between body mass index, waist circumference and erectile dysfunction: a systematic review and META-analysis

Growing evidence reports that obesity might play a role in erectile dysfunction (ED), but limited knowledge is available. We conducted a meta-analysis to estimate the prevalence of ED in overweight men and men with obesity. We performed a systematic review up to 01/04/2019 to investigate the associations between obesity and ED. Applying a random-effect model, we calculated the prevalence of ED, the odds ratio (OR) for the presence of ED by Body Mass Index (BMI) categories and the mean differences between ED and controls in BMI and Waist Circumference (WC). Among 3409 studies, we included 45 articles with 42,489 men (mean age = 55 years). Taking normal weight men as reference, the prevalence…

Physical activity, diet quality and all-cause cardiovascular disease and cancer mortality: A prospective study of 346 627 UK Biobank participants

ObjectivesTo examine independent and interactive associations of physical activity and diet with all-cause, cardiovascular disease (CVD) and physical activity, diet and adiposity-related (PDAR) cancer mortality.MethodsThis population-based prospective cohort study (n=346 627) is based on the UK Biobank data with linkage to the National Health Service death records to 30 April 2020. A left-truncated Cox proportional hazards model was fitted to examine the associations between exposures (self-reported total moderate-to-vigorous intensity physical activity (MVPA), vigorous-intensity physical activity (VPA) and a diet quality index (score ranged 0–3)) and outcomes (all-cause, CVD and PDAR cance…

The effects of graded caloric restriction: XII. Comparison of mouse to human impact on cellular senescence in the colon.

Calorie restriction (CR) is an effective strategy to delay the onset and progression of aging phenotypes in a variety of organisms. Several molecular players are involved in the anti-aging effects of CR, but mechanisms of regulation are poorly understood. Cellular senescence—a cellular state of irreversible growth arrest—is considered a basic mechanism of aging. Senescent cells accumulate with age and promote a number of age-related pathologies. Whether environmental conditions such as diet affect the accumulation of cellular senescence with age is still unclear. Here, we show that a number of classical transcriptomic markers of senescent cells are reduced in adult but relatively young mice…

Weight loss is associated with improvements in cognitive function among overweight and obese people: A systematic review and meta-analysis

Whilst obesity is associated with a higher risk of cognitive impairment, the influence of weight loss on cognitive function in obese/overweight people is equivocal. We conducted a meta-analysis of randomized controlled trials (RCTs) and longitudinal studies evaluating the influence of voluntary weight loss on cognitive function in obese/overweight individuals. Articles were acquired from a systematic search of major databases from inception till 01/2016. A random effect meta-analysis of weight loss interventions (diet, physical activity, bariatric surgery) on different cognitive domains (memory, attention, executive functions, language and motor speed) was conducted. Twenty studies (13 long…

Adherence to a healthy lifestyle and multiple sclerosis: a case–control study from the UK Biobank

Background: Multiple sclerosis (MS) is a common and disabling condition. The importance of healthy lifestyle for this disease is poorly explored. Objective: To test whether adherence to healthier lifestyle patterns is associated with a lower presence of multiple sclerosis (MS). Methods: By using a case–control design, we investigated the combined association of four healthy lifestyle-related factors (no current smoking, healthy diet, exercising regularly, body mass index <30 kg/m2) and the prevalence of MS. A logistic regression analysis, adjusted for potential confounders, was used and data reported as odds ratios (ORs) with their 95% confidence intervals (CIs). Results: 728 participant…

In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles

Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions. We studied plasma samples from men with prostate cancer awaiting prostatectomy who particip…

Combined associations of body weight and lifestyle factors with all cause and cause specific mortality in men and women: prospective cohort study

Objective  To evaluate the combined associations of diet, physical activity, moderate alcohol consumption, and smoking with body weight on risk of all cause and cause specific mortality. Design  Longitudinal study with up to 32 years of follow-up. Setting  Nurses’ Health Study (1980-2012) and Health Professionals Follow-up Study (1986-2012). Participants  74 582 women from the Nurses’ Health Study and 39 284 men from the Health Professionals Follow-up Study who were free from cardiovascular disease and cancer at baseline. Main outcome measures  Exposures included body mass index (BMI), score on the alternate healthy eating index, level of physical activity, smoking habits, and alcohol drink…

Aging and chronic inflammation: highlights from a multidisciplinary workshop

Abstract: Aging is a gradual, continuous series of natural changes in biological, physiological, immunological, environmental, psychological, behavioral, and social processes. Aging entails changes in the immune system characterized by a decrease in thymic output of naïve lymphocytes, an accumulated chronic antigenic stress notably caused by chronic infections such as cytomegalovirus (CMV), and immune cell senescence with acquisition of an inflammatory senescence-associated secretory phenotype (SASP). For this reason, and due to the SASP originating from other tissues, aging is commonly accompanied by low-grade chronic inflammation, termed “inflammaging”. After decades of accumulating evide…

Dietary protein restriction reduces circulating VLDL triglyceride levels via CREBH-APOA5-dependent and -independent mechanisms

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. Dietary interventions based on protein restriction (PR) reduce circulating triglycerides (TGs), but underlying mechanisms and clinical relevance remain unclear. Here, we show that 1 week of a protein-free diet without enforced calorie restriction significantly lowered circulating TGs in both lean and diet-induced obese mice. Mechanistically, the TG-lowering effect of PR was due, in part, to changes in very low-density lipoprotein (VLDL) metabolism both in liver and peripheral tissues. In the periphery, PR stimulated VLDL-TG consumption by increasing VLDL-bound APOA5 expression and promoting VLDL-TG hydrolysis and…

What are the roles of calorie restriction and diet quality in promoting healthy longevity?

Epidemiological and experimental data indicate that diet plays a central role in the pathogenesis of many age-associated chronic diseases, and in the biology of aging itself. Data from several animal studies suggest that the degree and time of calorie restriction (CR) onset, the timing of food intake as well as diet composition, play major roles in promoting health and longevity, breaking the old dogma that only calorie intake is important in extending healthy lifespan. Data from human studies indicate that long-term CR with adequate intake of nutrients results in several metabolic adaptations that reduce the risk of developing type 2 diabetes, hypertension, cardiovascular disease and cance…

Calorie restriction causes multiple beneficial metabolic adaptations linearly related with the degree of weight loss in non-obese individuals: Results of CALERIE, a multicenter randomised controlled trial

BACKGROUND & AIMS: Understanding the temporal association and relative power of anthropometric, body composition and energy metabolism measurements of calorie restriction (CR) in predicting metabolic and hormonal adaptations is important, given the clinical and public health implications of excess weight and adiposity. METHODS: Anthropometric (body weight, BMI, waist circumference), body composition (body fat and lean mass by DXA), energy metabolism (leptin and total daily energy intake by doubly labelled water [DLW]) markers and an extensive assessment of cardiometabolic, inflammatory and hormonal risk factors were obtained in 191, 21–50 year old non-obese (BMI 22·0–27·9 kg/m2) women a…