Publications by authors named "Bastian Kochlik"

12 Publications

  • Page 1 of 1

Altered Adiponectin Response in Older Women Following Dextrose and High-Fat Dietary Challenges.

Mol Nutr Food Res 2021 Jul 21:e2100487. Epub 2021 Jul 21.

German Institute of Human Nutrition, Potsdam - Rehbrücke, Department of Nutrition and Gerontology, Nuthetal, Germany.

Scope: Despite its beneficial properties, higher adiponectin concentrations are paradoxically associated with mortality in advanced age. Several mechanisms are being discussed. However, little is known about postprandial regulation of adiponectin in older adults. We assessed age-specific differences of the adiponectin response to different test meals considering potential determinants.

Methods And Results: Older (n = 20) and younger (n = 22) women were randomized to a dextrose (DEX) or high-fat (HF) dietary challenge. Postprandial adiponectin and fibroblast growth factor 21 (FGF21) concentrations were measured before and 60, 120, 240 min after ingestion. We assessed postprandial changes and group differences using linear mixed models controlled for possible determinants. In younger women, postprandial adiponectin remained stable after both test meals. In contrast, adiponectin increased following DEX and decreased after HF in older women, irrespective of control variables. Postprandial adiponectin was positively associated with malondialdehyde and inversely associated with interleukin-6 following DEX and also negatively associated with metabolic parameters after both test meals. In older women, elevated postprandial FGF21 concentrations were associated with a higher adiponectin response (β = 30.7, 95%CI 10.6; 50.8, p = 0.007).

Conclusions: Adiponectin response is associated with type of dietary challenge, age and FGF21 response. Age-group differences are partly attributable to metabolic parameters and oxidative stress. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/mnfr.202100487DOI Listing
July 2021

Postprandial dynamics and response of fibroblast growth factor 21 in older adults.

Clin Nutr 2021 Jun 27;40(6):3765-3771. Epub 2021 Apr 27.

German Institute of Human Nutrition, Potsdam-Rehbrücke, Department of Nutrition and Gerontology, Nuthetal, Germany; University of Potsdam, Institute of Nutritional Science, Potsdam, Germany; Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Geriatrics, Berlin, Germany. Electronic address:

Background & Aims: Fibroblast growth factor 21 (FGF21) plays a pivotal role in glucose and lipid metabolism and has been proposed as a longevity hormone. However, elevated plasma FGF21 concentrations are paradoxically associated with mortality in higher age and little is known about the postprandial regulation of FGF21 in older adults. In this parallel group study, we investigated postprandial FGF21 dynamics and response in older (65-85 years) compared to younger (18-35 years) adults following test meals with varying macronutrient composition.

Methods: Participants (n = 60 older; n = 60 younger) were randomized to one of four test meals: dextrose, high carbohydrate (HC), high fat (HF) or high protein (HP). Blood was drawn before and 15, 30, 60, 120, 240 min after meal ingestion. Postprandial dynamics were evaluated using repeated measures ANCOVA. FGF21 response was assessed by incremental area under the curve.

Results: Fasting FGF21 concentrations were significantly higher in older adults. FGF21 dynamics were affected by test meal (p < 0.001) and age (p = 0.013), when adjusted for BMI and fasting FGF21. Postprandial FGF21 concentrations steadily declined over 240 min in both age groups after HF and HP, but not after dextrose or HC ingestion. At 240 min, FGF21 concentrations were significantly higher in older than in younger adults following dextrose (133 pg/mL, 95%CI: 103, 172 versus 91.2 pg/mL, 95%CI: 70.4, 118; p = 0.044), HC (109 pg/mL, 95%CI: 85.1, 141 versus 70.3 pg/mL, 95%CI: 55.2, 89.6; p = 0.014) and HP ingestion (45.4 pg/mL, 95%CI: 34.4, 59.9 versus 27.9 pg/mL 95%CI: 20.9, 37.1; p = 0.018). FGF21 dynamics and response to HF were similar for both age groups.

Conclusions: The age-specific differences in postprandial FGF21 dynamics and response in healthy adults, potentially explain higher FGF21 concentrations in older age. Furthermore, there appears to be a significant impact of acute and recent protein intake on FGF21 secretion.
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http://dx.doi.org/10.1016/j.clnu.2021.04.037DOI Listing
June 2021

Medication Intake Is Associated with Lower Plasma Carotenoids and Higher Fat-Soluble Vitamins in the Cross-Sectional MARK-AGE Study in Older Individuals.

J Clin Med 2020 Jul 1;9(7). Epub 2020 Jul 1.

Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany.

The regular use of medication may interfere with micronutrient metabolism on several levels, such as absorption, turnover rate, and tissue distribution, and this might be amplified during aging. This study evaluates the impact of self-reported medication intake on plasma micronutrients in the MARK-AGE Project, a cross-sectional observational study in 2217 subjects (age- and sex-stratified) aged 35-75 years from six European countries that were grouped according to age. Polypharmacy as possible determinant of micronutrient concentrations was assessed using multiple linear regression models adjusted for age-group, dietary fruit, vegetables, and juice intake, and other confounders. Younger participants reported taking fewer drugs than older participants. Inverse associations between medication intake and lutein (-3.31% difference per increase in medication group), β-carotene (-11.44%), α-carotene (-8.50%) and positive associations with retinol (+2.26%), α-tocopherol/cholesterol (+2.89%) and γ-tocopherol/cholesterol (+1.36%) occurred in multiple adjusted regression models. Combined usage of a higher number of medical drugs was associated with poorer status of carotenoids on the one hand and higher plasma concentrations of retinol, α- and γ-tocopherol on the other hand. Our results raise concerns regarding the safety of drug combinations via the significant and surprisingly multifaceted disturbance of the concentrations of relevant micronutrients.
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http://dx.doi.org/10.3390/jcm9072072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408954PMC
July 2020

Quantifying technical confounders in microbiome studies.

Cardiovasc Res 2021 Feb;117(3):863-875

Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125 Berlin, Germany.

Aims: Recent technical developments have allowed the study of the human microbiome to accelerate at an unprecedented pace. Methodological differences may have considerable impact on the results obtained. Thus, we investigated how different storage, isolation, and DNA extraction methods can influence the characterization of the intestinal microbiome, compared to the impact of true biological signals such as intraindividual variability, nutrition, health, and demographics.

Methods And Results: An observative cohort study in 27 healthy subjects was performed. Participants were instructed to collect stool samples twice spaced by a week, using six different methods (naive and Zymo DNA/RNA Shield on dry ice, OMNIgene GUT, RNALater, 95% ethanol, Zymo DNA/RNA Shield at room temperature). DNA extraction from all samples was performed comparatively using QIAamp Power Fecal and ZymoBIOMICS DNA Kits. 16S rRNA sequencing of the gut microbiota as well as qPCRs were performed on the isolated DNA. Metrics included alpha diversity as well as multivariate and univariate comparisons of samples, controlling for covariate patterns computationally. Interindividual differences explained 7.4% of overall microbiome variability, whereas the choice of DNA extraction method explained a further 5.7%. At phylum level, the tested kits differed in their recovery of Gram-positive bacteria, which is reflected in a significantly skewed enterotype distribution.

Conclusion: DNA extraction methods had the highest impact on observed microbiome variability, and were comparable to interindividual differences, thus may spuriously mimic the microbiome signatures of various health and nutrition factors. Conversely, collection methods had a relatively small influence on microbiome composition. The present study provides necessary insight into the technical variables which can lead to divergent results from seemingly similar study designs. We anticipate that these results will contribute to future efforts towards standardization of microbiome quantification procedures in clinical research.
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http://dx.doi.org/10.1093/cvr/cvaa128DOI Listing
February 2021

Plasma carotenoids, tocopherols and retinol - Association with age in the Berlin Aging Study II.

Redox Biol 2020 05 13;32:101461. Epub 2020 Feb 13.

Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany; Geriatrics Research Group, Charité - Universitätsmedizin Berlin, 13347 Berlin, Germany; Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany. Electronic address:

Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micronutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, α-carotene, α-tocopherol, β-cryptoxanthin (only in women), and γ-tocopherol (only in men). β-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, α-carotene (both inverse), α-tocopherol, γ-tocopherol, and β-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for β-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and α-carotene concentration in older subjects, bioavailability studies in older participants are necessary.
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http://dx.doi.org/10.1016/j.redox.2020.101461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030983PMC
May 2020

Associations of fat-soluble micronutrients and redox biomarkers with frailty status in the FRAILOMIC initiative.

J Cachexia Sarcopenia Muscle 2019 12 21;10(6):1339-1346. Epub 2019 Aug 21.

Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany.

Background: A poor fat-soluble micronutrient (FMN) and a high oxidative stress status are associated with frailty. Our aim was to determine the cross-sectional association of FMNs and oxidative stress biomarkers [protein carbonyls (PrCarb) and 3-nitrotyrosine] with the frailty status in participants older than 65 years.

Methods: Plasma levels of vitamins A (retinol), D , E (α-tocopherol and γ-tocopherol) and carotenoids (α-carotene and β-carotene, lycopene, lutein/zeaxanthin, and β-cryptoxanthin), PrCarb, and 3-nitrotyrosine were measured in 1450 individuals of the FRAILOMIC initiative. Participants were classified into robust, pre-frail, and frail using Fried's frailty criteria. Associations between biomarkers and frailty status were assessed by general linear and logistic regression models, both adjusted for cohort, season of blood sampling, gender, age, height, weight, and smoking.

Results: Robust participants had significantly higher vitamin D and lutein/zeaxanthin concentrations than pre-frail and frail subjects; had significantly higher γ-tocopherol, α-carotene, β-carotene, lycopene, and β-cryptoxanthin concentrations than frail subjects, and had significantly lower PrCarb concentrations than frail participants in multivariate linear models. Frail subjects were more likely to be in the lowest than in the highest tertile for vitamin D (adjusted odds ratio: 2.15; 95% confidence interval: 1.42-3.26), α-tocopherol (2.12; 1.39-3.24), α-carotene (1.69; 1.00-2.88), β-carotene (1.84; 1.13-2.99), lycopene (1.94; 1.24-3.05), lutein/zeaxanthin (3.60; 2.34-5.53), and β-cryptoxanthin (3.02; 1.95-4.69) and were more likely to be in the highest than in the lowest tertile for PrCarb (2.86; 1.82-4.49) than robust subjects in multivariate regression models.

Conclusions: Our study indicates that both low FMN and high PrCarb concentrations are associated with pre-frailty and frailty.
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http://dx.doi.org/10.1002/jcsm.12479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6903435PMC
December 2019

Associations of Plasma 3-Methylhistidine with Frailty Status in French Cohorts of the FRAILOMIC Initiative.

J Clin Med 2019 Jul 10;8(7). Epub 2019 Jul 10.

Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany.

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.
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http://dx.doi.org/10.3390/jcm8071010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678434PMC
July 2019

Gender- and age-dependencies of oxidative stress, as detected based on the steady state concentrations of different biomarkers in the MARK-AGE study.

Redox Biol 2019 06 15;24:101204. Epub 2019 Apr 15.

Department of Physiology and Pharmacology, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Recently, Weber et al. published a thorough investigation of the age-dependency of oxidative stress (OS) determined by the steady state concentrations of different compounds - oxidation products and antioxidants - that are in common use as biomarkers of OS in 2207 healthy individuals of the cross-sectional MARK-AGE Project. The correlations among biomarkers were significant but weak. These findings may indicate different manifestations of OS and must further be evaluated. Here, we report a refined analysis of OS based on the above-mentioned original data. We show that malondialdehyde (MDA) appears to be sensitive to both gender and age. It is significantly lower and shows a greater age-dependence in women than in men. The age-dependency of MDA in women arises in a stepwise fashion. The age-dependent slope of the steady state concentration is maximal at the age between 50 and 55 years, indicating that it may be attributed to the change of metabolism in the post-menopause. Interestingly, total glutathione (GSH) decreased with age simultaneously with the increase in MDA. Different biomarkers yield different gender- and age-dependencies. Unlike the concentration of MDA, the concentrations of the other two oxidation products, i.e. protein carbonyls and 3-nitrotyrosine were similar in men and women and appeared to be independent of age in the healthy study population. The analyzed antioxidants exhibited different gender- and age-dependencies. In conclusion, it appears that all the biomarkers assessed here reflect different types of OS and that MDA and GSH reflect the same type of OS.
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http://dx.doi.org/10.1016/j.redox.2019.101204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477672PMC
June 2019

Methionine restriction prevents onset of type 2 diabetes in NZO mice.

FASEB J 2019 06 6;33(6):7092-7102. Epub 2019 Mar 6.

Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.

Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits increased circulating levels of FGF21 and merits further investigation.-Castaño-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schürmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.
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http://dx.doi.org/10.1096/fj.201900150RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529347PMC
June 2019

The Influence of Dietary Habits and Meat Consumption on Plasma 3-Methylhistidine-A Potential Marker for Muscle Protein Turnover.

Mol Nutr Food Res 2018 05 19;62(9):e1701062. Epub 2018 Apr 19.

Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, 14558, Germany.

Scope: 3-Methylhistidine (3-MH) as a potential biomarker for muscle protein turnover is influenced by meat intake but data on the impact of meat on plasma 3-MH are scarce. We determined the association of plasma 3-MH, 1-methylhistidine (1-MH), and creatinine with dietary habits and assessed the impact of a single white meat intervention during a meat-free period.

Methods And Results: Plasma 3-MH, 1-MH, and creatinine concentrations of healthy young omnivores (n = 19) and vegetarians (n = 16) were analyzed together with data on anthropometry, body composition, grip strength, and nutrition. After baseline measurements omnivores adhered to a meat-free diet for 6 days and received a defined administration of chicken breast on day four. At baseline, omnivores had higher plasma 3-MH and 1-MH concentrations than vegetarians. White meat administration led to a slight increase in plasma 3-MH in omnivores. The elevated 3-MH concentrations significantly declined within 24 h after white meat intake.

Conclusion: 1-MH concentrations in plasma seem to be suitable to display (white) meat consumption and its influence on 3-MH plasma concentration. 3-MH in plasma may be used as a biomarker for muscle protein turnover if subjects have not consumed meat in the previous 24 h.
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http://dx.doi.org/10.1002/mnfr.201701062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5969234PMC
May 2018

New findings of oxidative stress biomarkers in nutritional research.

Curr Opin Clin Nutr Metab Care 2017 Sep;20(5):349-359

aDepartment of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbruecke (DIfE) bNutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal cGerman Center for Diabetes Research (DZD), Munich dGerman Center for Cardiovascular Research (DZHK), Berlin, Germany *Bastian Kochlik and Daniela Weber contributed equally to the article.

Purpose Of Review: The aim of this article is to present a brief overview of recently published articles assessing oxidative stress markers in nutritional studies.

Recent Findings: Intervention and observational studies were carried out in both, healthy subjects and patients and describe the association of foodstuffs as well as isolated nutrients with biomarkers of oxidative stress. The results from human intervention studies on healthy participants and patients are controversial. Long-term interventions (>8 weeks) seem to be more effective than short-term or single-dose interventions. Results are difficult to compare because not only the methods used, also the assessed biomarkers and outcomes were very diverse. In addition, studies vary in the compounds and doses used, duration, participants and so on. Different biomarkers (damaged molecules together with antioxidants from different compartments) should be assessed to evaluate the true 'redox-status' of an individual and the impact of a nutritional intervention.

Summary: Both observational and interventional studies performed in healthy participants and patients show possible beneficial effects of nutrients and foodstuffs by improving oxidative stress markers and antioxidant enzyme activities. Biomarkers should be standardized to allow better comparison of results of antioxidant intervention studies.
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http://dx.doi.org/10.1097/MCO.0000000000000388DOI Listing
September 2017

Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence.

Redox Biol 2017 04 7;11:482-501. Epub 2016 Dec 7.

Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany; Faculty of Medicine, Department of Biomedicine, University of Porto, 4200-319, Portugal; Institute for Innovation and Health Research (I3S), Aging and Stress Group, R. Alfredo Allen, 4200-135 Porto, Portugal. Electronic address:

Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies) by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset.
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http://dx.doi.org/10.1016/j.redox.2016.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228102PMC
April 2017
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