Association of body mass index and waist circumference with successful ageing: 16 year follow-up of the Whitehall II study

Objective: We examined whether midlife body mass index (BMI) and waist circumference (WC) predict successful ageing. Design and Methods BMI/WC were assessed in 4869 persons (mean age 51.2, range 42–63 in 1991/93) and survival and successful ageing (alive, no chronic disease at age >60 years, not in the worst age- and sex-standardized quintile of cognitive, physical, respiratory, and cardiovascular, and mental health) ascertained over a 16-year follow-up, analysed using logistic regression adjusted for socio-demographic factors and health behaviours. Results: 507 participants died, 1008 met the criteria for successful ageing. Those with BMI≥30 kg/m2 had lower odds of successful ageing (Odds Ratio (OR)=0.37; 95% Confidence Interval (CI): 0.27, 0.50) and survival (OR=0.55; 95% CI: 0.41, 0.74) compared to BMI between 18.5–25 kg/m2. Those with a large waist circumference (≥102/88 cm in men/women) had lower odds of successful ageing (OR=0.41; 95% CI: 0.31, 0.54) and survival (OR=0.57; 95% CI: 0.44, 0.73) compared to those with a small waist (<94/80 cm in men/women). Analysis with finer categories showed lower odds of successful ageing starting at BMI ≥23.5 kg/m2 and waist circumference 82/68 cm in men/women. Conclusions: Optimal midlife BMI and waist circumference for successful ageing might be substantially below the current thresholds used to define obesity

Healthy behaviors at age 50 years and frailty at older ages in a 20-year follow-up of the UK Whitehall II cohort: A longitudinal study

Severine Sabia and colleagues investigate whether healthy behaviors at midlife are associated with reduced risk of frailty at older ages.Peer reviewe

1,25‐dihydroxyvitamin D 3 influences cellular homocysteine levels in murine preosteoblastic MC3T3‐E1 cells by direct regulation of cystathionine β‐synthase

High homocysteine (HCY) levels are a risk factor for osteoporotic fracture. Furthermore, bone quality and strength are compromised by elevated HCY owing to its negative impact on collagen maturation. HCY is cleared by cystathionine β‐synthase (CBS), the first enzyme in the transsulfuration pathway. CBS converts HCY to cystathionine, thereby committing it to cysteine synthesis. A microarray experiment on MC3T3‐E1 murine preosteoblasts treated with 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] revealed a cluster of genes including the cbs gene, of which the transcription was rapidly and strongly induced by 1,25(OH) 2 D 3 . Quantitative real‐time PCR and Western blot analysis confirmed higher levels of cbs mRNA and protein after 1,25(OH) 2 D 3 treatment in murine and human cells. Moreover, measurement of CBS enzyme activity and quantitative measurements of HCY, cystathionine, and cysteine concentrations were consistent with elevated transsulfuration activity in 1,25(OH) 2 D 3 ‐treated cells. The importance of a functional vitamin D receptor (VDR) for transcriptional regulation of cbs was shown in primary murine VDR knockout osteoblasts, in which upregulation of cbs in response to 1,25(OH) 2 D 3 was abolished. Chromatin immunoprecipitation on chip and transfection studies revealed a functional vitamin D response element in the second intron of cbs . To further explore the potential clinical relevance of our ex vivo findings, human data from the Longitudinal Aging Study Amsterdam suggested a correlation between vitamin D status [25(OH)D 3 levels] and HCY levels. In conclusion, this study showed that cbs is a primary 1,25(OH) 2 D 3 target gene which renders HCY metabolism responsive to 1,25(OH) 2 D 3 . © 2011 American Society for Bone and Mineral ResearchPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88106/1/493_ftp.pd

Dairy consumption and risk of frailty in older adults: A prospective cohort study

OBJECTIVES: To examine the association between consumption of dairy products and risk of frailty in community-dwelling older adults. DESIGN: Prospective cohort study. SETTING: General population from the older cohort of the Study on Nutrition and Cardiovascular Risk in Spain. PARTICIPANTS: Community-dwelling adults aged 60 and older free of frailty at baseline (N = 1,871). MEASUREMENTS: From 2008 to 2010, food consumption was assessed using a validated diet history. Participants were examined again in 2012 to assess incident frailty, defined as at least three of the five Fried criteria (exhaustion, weakness, low physical activity, slow walking speed, unintentional weight loss). Adjusted odds ratios (OR) for the main confounders were obtained using logistic regression. RESULTS: During follow-up, 134 new cases of frailty were identified. Participants consuming seven or more servings per week of low-fat milk and yogurt had lower incidence of frailty (OR = 0.52; 95% confidence interval (CI) = 0.29-0.90; P for trend = .03) than those consuming less than one serving per week. Specifically, consumers of seven or more servings per week of low-fat milk and yogurt had less risk of slow walking speed (OR = 0.64, 95% CI = 0.44-0.92, P trend = .01) and of weight loss (OR = 0.54, 95% CI = 0.33-0.87, P trend = .02). Consuming seven or more servings per week of whole milk or yogurt (OR = 1.53, 95% CI = 0.90-2.60, P trend = .10) or of cheese (OR = 0.91, 95% CI = 0.52-1.61; P trend = .61) was not associated with incident frailty. CONCLUSION: Higher consumption of low-fat milk and yogurt was associated with lower risk of frailty and, specifically, of slow walking speed and weight loss. Current recommendations to prevent frailty include protein supplementation; thus, although experimental research is needed, increasing the consumption of low-fat yogurt and milk might prevent frailty in older adultsThis work was supported by several sources: a) the Ministry of Health of Spain (FISS grants 09/1626, 09/0104, 12/1166 and 13/00288); b) the European Union FP7- HEALTH-2012-Proposal No: 305483-2 (FRAILOMIC Initiative) and c) Sanofi-Aventi

Decline in low-density lipoprotein cholesterol concentration: lipid-lowering drugs, diet, or physical activity? Evidence from the Whitehall II study

Objective To examine the association of lipid-lowering drugs, change in diet and physical activity with a decline in low-density lipoprotein (LDL) cholesterol in middle age.Design A prospective cohort study.Setting The Whitehall II study.Participants 4469 British civil servants (72% men) aged 39-62 years at baseline.Main Outcome Measure Change in LDL-cholesterol concentrations between the baseline (1991-3) and follow-up (2003-4).Results Mean LDL-cholesterol decreased from 4.38 to 3.52 mmol/l over a mean follow-up of 11.3 years. In a mutually adjusted model, a decline in LDL-cholesterol was greater among those who were taking lipid-lowering treatment at baseline (-1.14 mmol/l, n=34), or started treatment during the follow-up (-1.77 mmol/l, n=481) compared with untreated individuals (n=3954; p < 0.001); among those who improved their diet-especially the ratio of white to red meat consumption and the ratio of polyunsaturated to saturated fatty acids intake-(-0.07 mmol/l, n=717) compared with those with no change in diet (n=3071; p=0.03) and among those who increased physical activity (-0.10 mmol/l, n=601) compared with those with no change in physical activity (n=3312; p=0.005). Based on these estimates, successful implementation of lipid-lowering drug treatment for high-risk participants (n=858) and favourable changes in diet (n=3457) and physical activity (n=2190) among those with non-optimal lifestyles would reduce LDL-cholesterol by 0.90 to 1.07 mmol/l in the total cohort.Conclusions Both lipid-lowering pharmacotherapy and favourable changes in lifestyle independently reduced LDL-cholesterol levels in a cohort of middle-aged men and women, supporting the use of multifaceted intervention strategies for prevention

Effects of Body Composition, Leptin, and Adiponectin on Bone Mineral Density in Prepubertal Girls

Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls. Forty-eight prepubertal girls were classified into obese and control groups by body mass index. Serum leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral density was measured using dual energy radiography absorptiometry and body composition was measured using bioelectrical impedance analysis. Lean and fat mass, and leptin were positively correlated with bone mineral density. Lean mass was a positive independent predictor of femoral and L-spine bone mineral density. Serum leptin was a postivie independent predictor of femoral bone mineral density. Fat mass was a negative independent predictor of femoral bone mineral density. In prepubertal girls, lean mass has a favorable effect on bone mineral density. Fat mass seems not to protect the bone structure against osteoporosis, despite increased mechanical loading. Serum leptin may play a biological role in regulating bone metabolism

Comparison of Remifentanil and Fentanyl for Postoperative Pain Control after Abdominal Hysterectomy

Purpose: In this randomized, double-blind study, we investigated the analgesic efficacy and side effects of continuous constant-dose infusions of remifentanil after total abdominal hysterectomy and compared it to fentanyl. Materials and Methods: Fifty-six adult female patients scheduled for elective total abdominal hysterectomy were enrolled in this study. Patients were randomly assigned to two groups according to fentanyl (group F, n = 28) or remifentanil (group R, n = 28) for postoperative analgesia. Patients in group F were given fentanyl intravenously with an infusion rate of fentanyl 0.5 μg/kg/hr; group R was given remifentanil with an infusion rate of remifentanil 0.05 μg/kg/ min for 2 days. Pain intensity at rest, occurrence of postoperative nausea and vomiting (PONV), dizziness, pruritus, and respiratory depression were assessed 1 hr after arrival at the post-anesthesia care unit, at 6; 12; 24; and 48 hr postoperation and 6 hr post-infusion of the study drug. Pain was evaluated by using visual analogue scale (VAS; 0- 10). The time that patients first requested analgesics was recorded as well as additional analgesics and antiemetics. Results: There were no significant differences in VAS, time to first postoperative analgesics, and additional analgesics between the 2 groups. The incidences and severities of PONV and opioid related side effects were not different between the groups; however, there were 3 episodes (10.7%) of serious respiratory depression in group R. Conclusion: Continuous infusion technique of remifentanil did not reveal any benefits compared to fentanyl. Furthermore, it is not safe for postoperative analgesia in the general ward

Integrative Physiology: Defined Novel Metabolic Roles of Osteocalcin

The prevailing model of osteology is that bones constantly undergo a remodeling process, and that the differentiation and functions of osteoblasts are partially regulated by leptin through different central hypothalamic pathways. The finding that bone remodeling is regulated by leptin suggested possible endocrinal effects of bones on energy metabolism. Recently, a reciprocal relationship between bones and energy metabolism was determined whereby leptin influences osteoblast functions and, in turn, the osteoblast-derived protein osteocalcin influences energy metabolism. The metabolic effects of bones are caused by the release of osteocalcin into the circulation in an uncarboxylated form due to incomplete γ-carboxylation. In this regard, the Esp gene encoding osteotesticular protein tyrosine phosphatase is particularly interesting because it may regulate γ-carboxylation of osteocalcin. Novel metabolic roles of osteocalcin have been identified, including increased insulin secretion and sensitivity, increased energy expenditure, fat mass reduction, and mitochondrial proliferation and functional enhancement. To date, only a positive correlation between osteocalcin and energy metabolism in humans has been detected, leaving causal effects unresolved. Further research topics include: identification of the osteocalcin receptor; the nature of osteocalcin regulation in other pathways regulating metabolism; crosstalk between nutrition, osteocalcin, and energy metabolism; and potential applications in the treatment of metabolic diseases

Cyclical regulation of the insulin-like growth factor binding protein 3 gene in response to 1α,25-dihydroxyvitamin D3

The nuclear receptor vitamin D receptor (VDR) is known to associate with two vitamin D response element (VDRE) containing chromatin regions of the insulin-like growth factor binding protein 3 (IGFBP3) gene. In non-malignant MCF-10A human mammary cells, we show that the natural VDR ligand 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) causes cyclical IGFBP3 mRNA accumulation with a periodicity of 60 min, while in the presence of the potent VDR agonist Gemini the mRNA is continuously accumulated. Accordingly, VDR also showed cyclical ligand-dependent association with the chromatin regions of both VDREs. Histone deacetylases (HDACs) play an important role both in VDR signalling and in transcriptional cycling. From the 11 HDAC gene family members, only HDAC4 and HDAC6 are up-regulated in a cyclical fashion in response to 1α,25(OH)2D3, while even these two genes do not respond to Gemini. Interestingly, HDAC4 and HDAC6 proteins show cyclical VDR ligand-induced association with both VDRE regions of the IGFBP3 gene, which coincides with histone H4 deacetylation on these regions. Moreover, combined silencing of HDAC4 and HDAC6 abolishes the cycling of the IGFBP3 gene. We assume that due to more efficient VDR interaction, Gemini induces longer lasting chromatin activation and therefore no transcriptional cycling but monotonically increasing IGFBP3 mRNA. In conclusion, 1α,25(OH)2D3 regulates IGFBP3 transcription through short-term cyclical association of VDR, HDAC4 and HDAC6 to both VDRE-containing chromatin regions