Abstract For a long time non communicable diseases (NCDs) were discussed as burden of the developed world. Recent alarming data show a reverse trend and a dramatic increase of NCDs in the developing ...world, in particular in highly populated transition countries. This is true for the main mortality triggering diseases such as CVD, cancer or diabetes. Almost 4 out of 5 NCD based deaths happen in low- and middle income countries. This development is multi-factorial and is based on some main trends such as globalization, supermarket growth, rapid urbanization and increasingly sedentary lifestyles. The latter leads to overweight or obesity, which again promotes NCDs similar as high blood pressure, high cholesterol and elevated blood glucose. A high quality diet including functional food or functional ingredients, accompanied by physical activity and a non-smoking policy, is one of the most promising factors in primary and secondary prevention of NCDs.
Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment ...risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.
Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. ...Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.
The Recommended Daily Allowance (RDA) for protein intake in the adult population is widely promoted as 0.8 g · kg−1 · d−1. Aging may increase protein requirements, particularly to maintain muscle ...mass.
We investigated whether controlled protein consumption at the current RDA or twice the RDA (2RDA) affects skeletal muscle mass and physical function in elderly men.
In this parallel-group randomized trial, 29 men aged >70 y mean ± SD body mass index (in kg/m2): 28.3 ± 4.2 were provided with a complete diet containing either 0.8 (RDA) or 1.6 (2RDA) g protein · kg−1 · d−1, aimed to balance energy needs. Before treatment and after 10 wk of intervention, whole-body and appendicular lean mass were measured by using dual-energy X-ray absorptiometry. Knee-extension peak power was measured with dynamometry.
Both groups were found to have been in a moderate negative energy balance (mean ± SD RDA: 209 ± 213 kcal/d; 2RDA 145 ± 214 kcal/d; P= 0.427 for difference between the groups). In comparison with RDA, whole-body lean mass increased in 2RDA (P = 0.001; 1.49 ± 1.30 kg, P < 0.001 compared with −0.55 ± 1.49 kg, P = 0.149). This difference was mostly accounted for by an increase in trunk lean mass found in 2RDA (+1.39 ± 1.09 kg, P < 0.001). Appendicular lean mass also decreased in RDA compared with 2RDA (P = 0.022), driven by a reduction in RDA (−0.64 ± 0.91 kg, P = 0.005 compared with 0.11 ± 0.57 kg, P = 0.592). Adjusting for energy imbalances did not alter these findings. Knee-extension peak power was also differently affected (P = 0.012; 26.6 ± 47.7 W, P = 0.015 in 2RDA compared with −11.7 ± 31.0 W, P = 0.180 in RDA).
Consumption of a diet providing 2RDA for protein compared with the current guidelines was found to have beneficial effects on lean body mass and leg power in elderly men. These effects were not explained by differences in energy balance. This trial was registered at the Australia New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12616000310460.
The study was conducted to assess the content of tocopherols (α-, β-, γ- and δ-) and carotenoids (α- and β-carotene, zeaxanthin, lutein, cryptoxanthin and lycopene) in the unsaponifiable matter as ...well as the amount of total phenols of 10 different types of nuts. Tocopherols and carotenoids were analysed with HPLC, total phenols photometrically. The mean value of α-tocopherol equivalents ranged from non-detectable (macadamias) to 33.1
mg/100
g extracted oil (hazelnuts). Among all nuts, almonds and hazelnuts had the highest mean α-tocopherol content (24.2 and 31.4
mg/100
g extracted oil, respectively). β- and γ-tocopherols were prevalent in Brazil nuts, cashews, peanuts, pecans, pines, pistachios and walnuts. Mean values oscillated between 5.1 (cashews) and 29.3 (pistachios). Traces of δ-tocopherol (<4
mg/100
g extracted oil) were analysed in cashews, hazelnuts, peanuts, pecans, pines, pistachios and walnuts. There were no carotenoids detected in the tested nuts with the exception of pistachios. The mean content of total phenolics varied between 32
mg gallic acid equivalents/100
g (pines) and 1625
mg (walnuts). The results show the heterogenic amounts of antioxidants in nuts, which emphasises the recommendation of a mixed nuts intake.
An association between vitamin D level and muscle-related traits has been frequently reported. Vitamin D level is dependent on various factors such as sunlight exposure and nutrition. But also on ...genetic factors. We, therefore, hypothesize that single nucleotide polymorphisms (SNPs) within the vitamin D pathway-related genes could contribute to muscle mass and function via an impact on vitamin D level. However, the integration of studies investigating these issues is still missing. Therefore, this review aimed to systematically identify and summarize the available evidence on the association between SNPs within vitamin D pathway-related genes and vitamin D status as well as various muscle traits in healthy adults. The review has been registered on PROSPERO and was conducted following PRISMA guidelines. In total, 77 studies investigating 497 SNPs in 13 different genes were included, with significant associations being reported for 59 different SNPs. Variations in GC, CYP2R1, VDR, and CYP24A1 genes were reported most frequently, whereby especially SNPs in the GC (rs2282679, rs4588, rs1155563, rs7041) and CYP2R1 genes (rs10741657, rs10766197, rs2060793) were confirmed to be associated with vitamin D level in more than 50% of the respective studies. Various muscle traits have been investigated only in relation to four different vitamin D receptor (VDR) polymorphisms (rs7975232, rs2228570, rs1544410, and rs731236). Interestingly, all of them showed only very low confirmation rates (6-17% of the studies). In conclusion, this systematic review presents one of the most comprehensive updates of the association of SNPs in vitamin D pathway-related genes with vitamin D status and muscle traits in healthy adults. It might be used for selecting candidate SNPs for further studies, but also for personalized strategies in identifying individuals at risk for vitamin D deficiency and eventually for determining a potential response to vitamin D supplementation.
Circulating bilirubin is associated with reduced serum cholesterol concentrations in humans and in hyperbilirubinaemic Gunn rats. However, mechanisms contributing to hypocholesterolaemia remain ...unknown. Therefore, this study aimed to investigate cholesterol synthesis, transport and excretion in mutant Gunn rats. Adult Gunn and control rats were assessed for daily faecal sterol excretion using metabolic cages, and water was supplemented with 1‐13C‐acetate to determine cholesterol synthesis. Bile was collected to measure biliary lipid secretion. Serum and liver were collected for biochemical analysis and for gene/protein expression using RT‐qPCR and western blot, respectively. Additionally, serum was collected and analysed from juvenile rats. A significant interaction of sex, age and phenotype on circulating lipids was found with adult female Gunn rats reporting significantly lower cholesterol and phospholipids. Female Gunn rats also demonstrated elevated cholesterol synthesis, greater biliary lipid secretion and increased total faecal cholesterol and bile acid excretion. Furthermore, they possessed increased hepatic low‐density lipoprotein (LDL) receptor and SREBP2 expression. In contrast, there were no changes to sterol metabolism in adult male Gunn rats. This is the first study to demonstrate elevated faecal sterol excretion in female hyperbilirubinaemic Gunn rats. Increased sterol excretion creates a negative intestinal sterol balance that is compensated for by increased cholesterol synthesis and LDL receptor expression. Therefore, reduced circulating cholesterol is potentially caused by increased hepatic uptake via the LDL receptor. Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).
Key points
Female adult hyperbilirubinaemic (Gunn) rats demonstrated lower circulating cholesterol, corroborating human studies that report a negative association between bilirubin and cholesterol concentrations.
Furthermore, female Gunn rats had elevated sterol excretion creating a negative intestinal sterol balance that was compensated for by elevated cholesterol synthesis and increased hepatic low‐density lipoprotein (LDL) receptor expression.
Therefore, elevated LDL receptor expression potentially leads to reduced circulating cholesterol levels in female Gunn rats providing an explanation for the hypocholesterolaemia observed in humans with elevated bilirubin levels.
This study also reports a novel interaction of sex with the hyperbilirubinaemic phenotype on sterol metabolism because changes were only reported in females and not in male Gunn rats.
Future studies are required to further evaluate the sexual dimorphism of this response and whether similar findings occur in females with benign unconjugated hyperbilirubinaemia (Gilbert's syndrome).
figure legend Female Gunn rats have an unconjugated hyperbilirubinaemia because of dysfunctional UGT1A1 enzyme function. Through an unknown mechanism, UGT1A1 dysfunction and/or elevated unconjugated bilirubin concentrations lead to increased faecal sterol excretion. Increased sterol outflow is potentially compensated by increased SREBP2‐mediated cholesterol synthesis and LDL receptor expression, ultimately contributing to reduced circulating cholesterol concentrations.
Scope
Oxidative imbalance plays a key role in cancer induction and cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). The aim of this study is to find out if gallic acid ...(GA) prevents oxidative stress in diabetic patients. Therefore, we investigate its impact on oxidation of DNA bases and on other health‐related macromolecules.
Methods and results
We perform an intervention study (n = 19) with GA and monitored alterations of the DNA stability in single cell gel electrophoresis (SCGE) assays in lymphocytes. Furthermore, a panel of health‐related biomarkers is measured before and after consumption of GA (15 mg p–1 d–1) for 7 d. Significant reduction of oxidized purines (by 31%, p < 0.001, effect size 0.404) and pyrimidines (by 2%, p < 0.022, effect size 0.089) is observed in SCGE assays. Furthermore, the plasma concentrations of oxidized‐LDL and C‐reactive protein are reduced after the intervention by 24% (p = 0.014, effect size 0.384) and 39% (p < 0.001, effect size 0.686), respectively. No alterations of other biomarkers are found.
Conclusions
A small amount of GA (in the range of daily consumption in Central Europe) prevents oxidative DNA damage and reduces markers which reflect inflammation and increased risks of cancer and CVD.
•Gallic acid (GA) supplementation over 7 d reduced oxidized purines in lymphocytes of T2DM patients.
•Oxo‐LDL was reduced by 24% in plasma after supplementation with GA.
•C‐reactive protein was reduced by 39% in plasma after supplementation.
•GA may contribute to the prevention of diabetes associated diseases.
There is an ongoing debate as to the optimal protein intake in older adults. An increasing body of experimental studies on skeletal muscle protein metabolism as well as epidemiological data suggest ...that protein requirements with ageing might be greater than many current dietary recommendations. Importantly, none of the intervention studies in this context specifically investigated very old individuals. Data on the fastest growing age group of the oldest old (aged 85 years and older) is very limited. In this review, we examine the current evidence on protein intake for preserving muscle mass, strength and function in older individuals, with emphasis on data in the very old. Available observational data suggest beneficial effects of a higher protein intake with physical function in the oldest old. Whilst, studies estimating protein requirements in old and very old individuals based on whole-body measurements, show no differences between these sub-populations of elderly. However, small sample sizes preclude drawing firm conclusions. Experimental studies that compared muscle protein synthetic (MPS) responses to protein ingestion in young and old adults suggest that a higher relative protein intake is required to maximally stimulate skeletal muscle MPS in the aged. Although, data on MPS responses to protein ingestion in the oldest old are currently lacking. Collectively, the data reviewed for this article support the concept that there is a close interaction of physical activity, diet, function and ageing. An attractive hypothesis is that regular physical activity may preserve and even enhance the responsiveness of ageing skeletal muscle to protein intake, until very advanced age. More research involving study participants particularly aged ≥85 years is warranted to better investigate and determine protein requirements in this specific growing population group.
Hyperbilirubinemia is a well-known condition in the clinical setting; however, the causes of elevated serum bilirubin are diverse, as are the clinical ramifications of this condition. For example, ...diagnoses of individuals vary depending on whether they exhibit an unconjugated or conjugated hyperbilirubinemia. Diagnoses can include conditions of disordered bilirubin metabolism (Gilbert's, Crigler-Najjar, Rotor, or Dubin-Johnson syndromes) or an acquired disease, including alcoholic/non-alcoholic fatty liver disease, hepatotropic hepatitis, cirrhosis, or hepato-biliary malignancy. Assessment of bilirubin concentrations is typically conducted as part of routine liver function testing. Mildly elevated total bilirubin with normal serum activities of liver transaminases, biliary damage markers, and red blood cell counts, however, may indicate the presence of Gilbert's syndrome (GS), a benign condition that is present in ∼5-10% of the population. In this case, mildly elevated unconjugated bilirubin in GS is strongly associated with "reduced" prevalence of chronic diseases, particularly cardiovascular diseases (CVD) and type 2 diabetes mellitus (and associated risk factors), as well as CVD-related and all-cause mortality. These reports challenge the dogma that bilirubin is simply a potentially neurotoxic by-product of heme catabolism and emphasize the importance of understanding its potential beneficial physiologic and detrimental pathophysiologic effects, in order to appropriately consider bilirubin test results within the clinical laboratory setting. With this information, we hope to improve the understanding of disorders of bilirubin metabolism, emphasize the diagnostic importance of these conditions, and outline the potential impact GS may have on resistance to disease.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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