Special Issue "Metabolomics to Probe Metabolism in Ageing and Age-related Neurodegenerative Diseases"

A special issue of Metabolites (ISSN 2218-1989).

Deadline for manuscript submissions: closed (30 September 2019).

Special Issue Editor

Dr. Julijana Ivanišević
E-Mail Website
Guest Editor
University of Lausanne, Faculty of Biology and Medicine, Lausanne, Switzerland
Interests: Metabolite role and activity; metabolic phenotyping of human population; quantitative metabolomic and lipidomic approaches; sexual dimorphism in metabolism; stratified and personalized approach to medicine
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Special Issue Information

Dear Colleagues,

Today’s ageing society is confronted with an epidemic of metabolic diseases, among which the neurodegenerative diseases present an ever-growing medical and social burden. Neurodegeneration has only recently been identified as an energy metabolism disorder, whose progress is related to ageing and a chronic inflammation process (i.e. Alzheimer’s disease). Although ageing is a major risk factor for neurodegeneration, several external and internal environmental exposures, such as nutrition, oxidative stress and the microbiome, have been proven to influence the onset and progression of metabolic alterations and inflammation in neurodegenerative diseases.

Metabolomics has evolved as an integrated technology that includes biomarker discovery, pathway analysis and phenotypic control, and is thus emerging for the investigation and prospective modulation of metabolism in ageing and age-related metabolic diseases, such as neurodegenerative disorders. Due to their high-throughput and sensitivity to assess the phenotypic alterations at the molecular level, metabolomic approaches can be applied from model systems, from neuronal cell cultures and brain organoids to large-scale human population studies. They allow us to measure and monitor over time the systemic (i.e. circulating blood) and central nervous (i.e. CSF, brain tissue) effects of disease on energy production and storage as well as signaling pathways. These metabolic changes can further be examined as a function of sex, ageing, diet, physical activity, cognitive decline, inflammation process, etc., to gain additional insights into disease pathogenesis.

The topics to be covered in this Special Issue include the metabolomics-led discoveries and metabolomics-assisted mechanistic studies that enhance our understanding of ageing and age-related neurodegenerative diseases, from model systems to human population studies. Manuscripts that uncover the physiological roles of endogenous metabolites and their capacity to modulate the ageing (i.e NAD+ metabolism) and neurodegenerative disease phenotype are strongly encouraged.

Dr. Julijana Ivanišević
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Metabolic Drift in Ageing
  • Ageing and Neurodegeneration as Metabolic Disorders
  • Neurodegeneration and Inflammation
  • Metabolomics-Led Discoveries in Ageing and Age-Related Neurodegenerative Diseases
  • Metabolomics-Assisted Mechanistic Studies in Ageing and Age-Related Neurodegenerative Diseases
  • Metabolomics Applied from Model Systems to Human Population Studies
  • Quantitative Metabolomic Approaches
  • Metabolite Activity to Modulate Metabolism

Published Papers (4 papers)

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Research

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Open AccessArticle
Effects of Aging and Methionine Restriction on Rat Kidney Metabolome
Metabolites 2019, 9(11), 280; https://doi.org/10.3390/metabo9110280 - 14 Nov 2019
Abstract
Methionine restriction (MetR) in animal models extends maximum longevity and seems to promote renoprotection by attenuating kidney injury. MetR has also been proven to affect several metabolic pathways including lipid metabolism. However, there is a lack of studies about the effect of MetR [...] Read more.
Methionine restriction (MetR) in animal models extends maximum longevity and seems to promote renoprotection by attenuating kidney injury. MetR has also been proven to affect several metabolic pathways including lipid metabolism. However, there is a lack of studies about the effect of MetR at old age on the kidney metabolome. In view of this, a mass spectrometry-based high-throughput metabolomic and lipidomic profiling was undertaken of renal cortex samples of three groups of male rats—An 8-month-old Adult group, a 26-month-old Aged group, and a MetR group that also comprised of 26-month-old rats but were subjected to an 80% MetR diet for 7 weeks. Additionally, markers of mitochondrial stress and protein oxidative damage were analyzed by mass spectrometry. Our results showed minor changes during aging in the renal cortex metabolome, with less than 59 differential metabolites between the Adult and Aged groups, which represents about 4% of changes in the kidney metabolome. Among the compounds identified are glycerolipids and lipid species derived from arachidonic acid metabolism. MetR at old age preferentially induces lipid changes affecting glycerophospholipids, docosanoids, and eicosanoids. No significant differences were observed between the experimental groups in the markers of mitochondrial stress and tissue protein damage. More than rejuvenation, MetR seems to induce a metabolic reprogramming. Full article
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Open AccessArticle
Oxylipin Profiling of Alzheimer’s Disease in Nondiabetic and Type 2 Diabetic Elderly
Metabolites 2019, 9(9), 177; https://doi.org/10.3390/metabo9090177 - 05 Sep 2019
Abstract
Oxygenated lipids, called “oxylipins,” serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) [...] Read more.
Oxygenated lipids, called “oxylipins,” serve a variety of important signaling roles within the cell. Oxylipins have been linked to inflammation and vascular function, and blood patterns have been shown to differ in type 2 diabetes (T2D). Because these factors (inflammation, vascular function, diabetes) are also associated with Alzheimer’s disease (AD) risk, we set out to characterize the serum oxylipin profile in elderly and AD subjects to understand if there are shared patterns between AD and T2D. We obtained serum from 126 well-characterized, overnight-fasted elderly individuals who underwent a stringent cognitive evaluation and were determined to be cognitively healthy or AD. Because the oxylipin profile may also be influenced by T2D, we assessed nondiabetic and T2D subjects separately. Within nondiabetic individuals, cognitively healthy subjects had higher levels of the nitrolipid 10-nitrooleate (16.8% higher) compared to AD subjects. AD subjects had higher levels of all four dihydroxyeicosatrienoic acid (DiHETrE) species: 14,15-DiHETrE (18% higher), 11,12 DiHETrE (18% higher), 8,9-DiHETrE (23% higher), and 5,6-DiHETrE (15% higher). Within T2D participants, we observed elevations in 14,15-dihydroxyeicosa-5,8,11-trienoic acid (14,15-DiHETE; 66% higher), 17,18-dihydroxyeicosa-5,8,11,14-tetraenoic acid (17,18-DiHETE; 29% higher) and 17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid (17-HDoHE; 105% higher) and summed fatty acid diols (85% higher) in subjects with AD compared to cognitively healthy elderly, with no differences in the DiHETrE species between groups. Although these effects were no longer significant following stringent adjustment for multiple comparisons, the consistent effects on groups of molecules with similar physiological roles, as well as clear differences in the AD-related profiles within nondiabetic and T2D individuals, warrant further research into these molecules in the context of AD. Full article
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Open AccessArticle
Non-Alcoholic Fatty Liver Disease, and the Underlying Altered Fatty Acid Metabolism, Reveals Brain Hypoperfusion and Contributes to the Cognitive Decline in APP/PS1 Mice
Metabolites 2019, 9(5), 104; https://doi.org/10.3390/metabo9050104 - 25 May 2019
Cited by 1
Abstract
Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease, is associated with cognitive decline in middle-aged adults, but the mechanisms underlying this association are not clear. We hypothesized that NAFLD would unveil the appearance of brain hypoperfusion in association with [...] Read more.
Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease, is associated with cognitive decline in middle-aged adults, but the mechanisms underlying this association are not clear. We hypothesized that NAFLD would unveil the appearance of brain hypoperfusion in association with altered plasma and brain lipid metabolism. To test our hypothesis, amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mice were fed a standard diet or a high-fat, cholesterol and cholate diet, inducing NAFLD without obesity and hyperglycemia. The diet-induced NAFLD disturbed monounsaturated and polyunsaturated fatty acid (MUFAs, PUFAs) metabolism in the plasma, liver, and brain, and particularly reduced n-3 PUFAs levels. These alterations in lipid homeostasis were associated in the brain with an increased expression of Tnfα, Cox2, p21, and Nox2, reminiscent of brain inflammation, senescence, and oxidative stress. In addition, compared to wild-type (WT) mice, while brain perfusion was similar in APP/PS1 mice fed with a chow diet, NAFLD in APP/PS1 mice reveals cerebral hypoperfusion and furthered cognitive decline. NAFLD reduced plasma β40- and β42-amyloid levels and altered hepatic but not brain expression of genes involved in β-amyloid peptide production and clearance. Altogether, our results suggest that in a mouse model of Alzheimer disease (AD) diet-induced NAFLD contributes to the development and progression of brain abnormalities through unbalanced brain MUFAs and PUFAs metabolism and cerebral hypoperfusion, irrespective of brain amyloid pathology that may ultimately contribute to the pathogenesis of AD. Full article
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Review

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Open AccessReview
Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics
Metabolites 2019, 9(12), 301; https://doi.org/10.3390/metabo9120301 - 13 Dec 2019
Abstract
Metabolomics is the latest ‘omics’ technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, [...] Read more.
Metabolomics is the latest ‘omics’ technology and systems biology science that allows for comprehensive profiling of small-molecule metabolites in biological systems at a specific time and condition. Metabolites are cellular intermediate products of metabolic reactions, which reflect the ultimate response to genomic, transcriptomic, proteomic, or environmental changes in a biological system. Aging is a complex biological process that is characterized by a gradual and progressive decline in molecular, cellular, tissue, organ, and organismal functions, and it is influenced by a combination of genetic, environmental, diet, and lifestyle factors. The precise biological mechanisms of aging remain unknown. Metabolomics has emerged as a powerful tool to characterize the organism phenotypes, identify altered metabolites, pathways, novel biomarkers in aging and disease, and offers wide clinical applications. Here, I will provide a comprehensive overview of our current knowledge on metabolomics led studies in aging with particular emphasis on studies leading to biomarker discovery. Based on the data obtained from model organisms and humans, it is evident that metabolites associated with amino acids, lipids, carbohydrate, and redox metabolism may serve as biomarkers of aging and/or longevity. Current challenges and key questions that should be addressed in the future to advance our understanding of the biological mechanisms of aging are discussed. Full article
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