J Clin Med

Frailty and sarcopenia are characterized by a loss of muscle mass and functionality and are diagnosed mainly by functional tests and imaging parameters. However, more muscle specific biomarkers are needed to improve frailty diagnosis. Plasma 3-methylhistidine (3-MH), as well as the 3-MH-to-creatinine (3-MH/Crea) and 3-MH-to-estimated glomerular filtration rate (3-MH/eGFR) ratios might support the diagnosis of frailty. Therefore, we investigated the cross-sectional associations between plasma 3-MH, 3-MH/Crea and 3-MH/eGFR with the frailty status of community-dwelling individuals (>65 years). 360 participants from two French cohorts of the FRAILOMIC initiative were classified into robust, pre-frail and frail according to Fried's frailty criteria. General linear models as well as bivariate and multiple linear and logistic regression models, which were adjusted for several confounders, were applied to determine associations between biomarkers and frailty status. The present study consisted of 37.8% robust, 43.1% pre-frail and 19.2% frail participants. Frail participants had significantly higher plasma 3-MH, 3-MH/Crea and 3-MH/eGFR ratios than robust individuals, and these biomarkers were positively associated with frailty status. Additionally, the likelihood to be frail was significantly higher for every increase in 3-MH (1.31-fold) and 3-MH/GFR (1.35-fold) quintile after adjusting for confounders. We conclude that 3-MH, 3-MH/Crea and 3-MH/eGFR in plasma might be potential biomarkers to identify frail individuals or those at higher risk to be frail, and we assume that there might be biomarker thresholds to identify these individuals. However, further, especially longitudinal studies are needed

Blood circulating miR-28-5p and let-7d-5p associate with premature ageing in Down syndrome

Persons with Down syndrome (DS) undergo a premature ageing with early onset of age-related diseases. The main endpoint of this study was the identification of blood circulating microRNAs (c-miRs) signatures characterizing DS ageing process. A discovery phase based on array was performed in plasma samples obtained from 3 young (31 ± 2 years-old) and 3 elderly DS persons (66 ± 2 years-old). Then, a validation phase was carried out for relevant miRs by RT-qPCR in an enlarged cohort of 43 DS individuals (from 19 up to 68 years-old). A group of 30 non-trisomic subjects, as representative of physiological ageing, was compared. In particular miR-628-5p, miR-152-3p, miR-28-5p, and let-7d-5p showed a lower level in younger DS persons (age ≤ 50 years) respect to the age-matched controls. Among those, miR-28-5p and let-7d-5p were found significantly decreased in physiological ageing ( oldest group ), thus they emerged as possible biomarkers of premature ageing in DS. Moreover, measuring blood levels of beta amyloid peptides, Aβ-42 was assessed at the lowest levels in physiological ageing and correlated with miR-28-5p and let-7d-5p in DS, while Aβ-40 correlated with miR-628-5p in the same cohort. New perspectives in terms of biomarkers are discussed

Considerations for a European animal welfare standard to evaluate adverse phenotypes in teleost fish

No abstract available

Protein carbonylation and aggregation precede neuronal apoptosis induced by partial glutathione depletion

While the build-up of oxidized proteins within cells is believed to be toxic, there is currently no evidence linking protein carbonylation and cell death. In the present study, we show that incubation of nPC12 (neuron-like PC12) cells with 50 μM DEM (diethyl maleate) leads to a partial and transient depletion of glutathione (GSH). Concomitant with GSH disappearance there is increased accumulation of PCOs (protein carbonyls) and cell death (both by necrosis and apoptosis). Immunocytochemical studies also revealed a temporal/spatial relationship between carbonylation and cellular apoptosis. In addition, the extent of all three, PCO accumulation, protein aggregation and cell death, augments if oxidized proteins are not removed by proteasomal degradation. Furthermore, the effectiveness of the carbonyl scavengers hydralazine, histidine hydrazide and methoxylamine at preventing cell death identifies PCOs as the toxic species. Experiments using well-characterized apoptosis inhibitors place protein carbonylation downstream of the mitochondrial transition pore opening and upstream of caspase activation. While the study focused mostly on nPC12 cells, experiments in primary neuronal cultures yielded the same results. The findings are also not restricted to DEM-induced cell death, since a similar relationship between carbonylation and apoptosis was found in staurosporine- and buthionine sulfoximine-treated nPC12 cells. In sum, the above results show for the first time a causal relationship between carbonylation, protein aggregation and apoptosis of neurons undergoing oxidative damage. To the best of our knowledge, this is the first study to place direct (oxidative) protein carbonylation within the apoptotic pathway

Effects of diets high in animal or plant protein on oxidative stress in individuals with type 2 diabetes: a randomized clinical trial

High-protein diet is a promising strategy for diabetes treatment supporting body weight control, improving glycaemic status, cardiovascular risk factors and reducing liver fat. Here, we investigated effects of diets high in animal (AP) or plant (PP) protein on oxidative stress and antioxidant status in individuals with type 2 diabetes (T2DM). 37 obese individuals (age 64.3 ± 1.0 years) with T2DM were randomized to an isocaloric diet (30 energy(E)% protein, 30E% fat and 40E% carbohydrates) rich in AP or PP for 6 weeks. Markers of oxidative and nitrosative stress and antioxidant status in plasma and nitrate/nitrite levels in urine were assessed. Gene expression in subcutaneous adipose tissue (SAT) was analyzed by RNA-Seq and real-time PCR.Both AP and PP diets similarly reduced plasma levels of malondialdehyde (P(AP) = 0.003, P(PP) = 1.6x10(-4)) and protein carbonyls (P(AP) = 1.2x10(-4), P(PP) = 3.0x10(-5)) over 6 weeks. Nitrotyrosine (NT) increased upon both AP and PP diets (PAP = 0.005,PPP = 0.004). SAT expression of genes involved in nitric oxide (NO) and oxidative stress metabolism and urine NO metabolite (nitrate/nitrite) levels were not changed upon both diets. Plasma levels of carotenoids increased upon PP diet, whereas retinol, alpha- and gamma-tocopherol slightly decreased upon both diets. AP and PP diets similarly improve oxidative stress but increase nitrosative stress markers in individuals with T2DM. Mechanisms of the NT regulation upon high-protein diets need further investigation

Invest Ophthalmol Vis Sci

Purpose: We investigated the cross-sectional associations between macular pigment optical density (MPOD), plasma lutein (L), and zeaxanthin (Z) concentrations and cognitive function in 184 older adults of the 3-City-Bordeaux cohort. Methods: MPOD was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma L and Z (L+Z) concentrations were determined by high-performance liquid chromatography and were considered either crude or expressed as a ratio of the concentration of plasma lipids (total cholesterol [TC] + triglycerides [TG]). Cognitive performances were assessed using the following four separate neuropsychological tests: the Mini-Mental State Examination (MMSE), the Isaacs Set Test (IST), the Benton Visual Retention Test (BVRT), and the sum of the three free recalls of the Free and Cued Selective Reminding Test (FCSRT). These test results were summarized by a composite global cognitive z-score. Results: Higher MPOD at 0.5 degrees was significantly associated with a higher composite z-score (beta = 0.15, 95% confidence interval [CI] 0.04-0.26), higher BVRT (beta = 0.39, 95%CI 0.08-0.70), and higher IST (beta = 1.16, 95%CI 0.11-2.22) performances. Higher plasma L+Z concentrations were significantly associated with higher IST scores (beta = 0.97, 95%CI 0.01-1.94). Furthermore, a higher L+Z/TC+TG ratio was associated with a higher composite z-score (beta = 0.12, 95%CI 0.01-0.23), along with higher IST (beta = 1.02, 95%CI 0.002-2.04) and FCSRT (beta = 1.55, 95%CI 0.41-2.69) performances. Conclusions: This analysis suggested that both higher MPOD and L+Z concentrations were significantly associated with higher cognitive performances. However, MPOD measurements have the advantage of being a fast and representative measure of long-term carotenoid intake

Clinical relevance of biomarkers of oxidative stress

SIGNIFICANCE Oxidative stress is considered to be an important component of various diseases. A vast number of methods have been developed and used in virtually all diseases to measure the extent and nature of oxidative stress, ranging from oxidation of DNA to proteins, lipids, and free amino acids. Recent Advances: An increased understanding of the biology behind diseases and redox biology has led to more specific and sensitive tools to measure oxidative stress markers, which are very diverse and sometimes very low in abundance. CRITICAL ISSUES The literature is very heterogeneous. It is often difficult to draw general conclusions on the significance of oxidative stress biomarkers, as only in a limited proportion of diseases have a range of different biomarkers been used, and different biomarkers have been used to study different diseases. In addition, biomarkers are often measured using nonspecific methods, while specific methodologies are often too sophisticated or laborious for routine clinical use. FUTURE DIRECTIONS Several markers of oxidative stress still represent a viable biomarker opportunity for clinical use. However, positive findings with currently used biomarkers still need to be validated in larger sample sizes and compared with current clinical standards to establish them as clinical diagnostics. It is important to realize that oxidative stress is a nuanced phenomenon that is difficult to characterize, and one biomarker is not necessarily better than others. The vast diversity in oxidative stress between diseases and conditions has to be taken into account when selecting the most appropriate biomarker. Antioxid. Redox Signal. 00, 000-000

Molecular strategies to prevent, inhibit and degrade advanced glycoxidation and advanced lipoxidation end products

The advanced glycoxidation end products (AGEs) and lipoxidation end products (ALEs) contribute to the development of diabetic complications and of other pathologies. The review discusses the possibilities of counteracting the formation and stimulating the degradation of these species by pharmaceuticals and natural compounds. The review discusses inhibitors of ALE and AGE formation, cross-link breakers, ALE/AGE elimination by enzymes and proteolytic systems, receptors for advanced glycation end products (RAGEs) and blockade of the ligand-RAGE axis

Robot life: simulation and participation in the study of evolution and social behavior.

This paper explores the case of using robots to simulate evolution, in particular the case of Hamilton's Law. The uses of robots raises several questions that this paper seeks to address. The first concerns the role of the robots in biological research: do they simulate something (life, evolution, sociality) or do they participate in something? The second question concerns the physicality of the robots: what difference does embodiment make to the role of the robot in these experiments. Thirdly, how do life, embodiment and social behavior relate in contemporary biology and why is it possible for robots to illuminate this relation? These questions are provoked by a strange similarity that has not been noted before: between the problem of simulation in philosophy of science, and Deleuze's reading of Plato on the relationship of ideas, copies and simulacra