Changes in levels of the antioxidant glutathione in brain and blood across the age span of healthy adults: A systematic review DOI Creative Commons
Flavie Detcheverry, Sneha Senthil, Sridar Narayanan

et al.

NeuroImage Clinical, Journal Year: 2023, Volume and Issue: 40, P. 103503 - 103503

Published: Jan. 1, 2023

Aging is characterized by a gradual decline of the body's biological functions, which can lead to increased production reactive oxygen species (ROS). Antioxidants neutralize ROS and maintain balance between oxidation reduction. If exceeds ability antioxidant systems neutralize, damaging state oxidative stress (OS) may exist. The reduced form glutathione (GSH) most abundant antioxidant, GSH considered marker OS. Our review summarizes literature on variations with age in healthy adults brain (in vivo, ex vivo) blood (plasma, serum), reliability vivo magnetic resonance spectroscopy (MRS) measurement GSH. A systematic PubMed search identified 35 studies. All MRS studies (N=13) reported good excellent reproducibility measures. In brain, 3 out 4 decreased age, measured precuneus, cingulate, occipital regions, while 1 study frontal sensorimotor regions. post-mortem studies, 2 hippocampal region. Oxidized disulfide (GSSG) was be caudate study, suggesting stress. Although findings lacked clear consensus, majority suggested age. low number (particularly potential regional differences have contributed variability brain. blood, contrast, levels predominately were decrease advancing (except oldest-old, who represent select group particularly successful agers), GSSG consensus. larger assessing age-specific level changes (N=16) allowed for more robust consensus across than Overall, suggests that aging associated OS body, but timing distribution require further study. contribution aging, effect interventions raise function, remain understudied. Given reliable tools measure exist, we hope this paper will serve as catalyst stimulate work field.

Language: Английский

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases DOI Creative Commons
Jian Sheng Loh, Wen Qi Mak, Li Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

Abstract The human gastrointestinal tract is populated with a diverse microbial community. vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect biology, including health maintenance, development, aging, disease. advent new sequencing technologies culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations shed light on microbiome–host interactions. Evidence unveiled bidirectional communication between central nervous system, referred as “microbiota–gut–brain axis”. microbiota–gut–brain axis represents an important regulator glial functions, making it actionable target ameliorate development progression neurodegenerative diseases. In this review, we discuss mechanisms As provides essential cues microglia, astrocytes, oligodendrocytes, examine communications microbiota these cells during healthy states Subsequently, diseases using metabolite-centric approach, while also examining role microbiota-related neurotransmitters hormones. Next, targeting intestinal barrier, blood–brain meninges, peripheral immune system counteract dysfunction neurodegeneration. Finally, conclude by assessing pre-clinical clinical evidence probiotics, prebiotics, fecal transplantation A thorough comprehension will foster effective therapeutic interventions for management

Language: Английский

Citations

255
Biomarkers of aging DOI Open Access

Hainan Bao,

Jiani Cao, Mengting Chen

et al.

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(5), P. 893 - 1066

Published: April 11, 2023

Language: Английский

Citations

203
Biological aging processes underlying cognitive decline and neurodegenerative disease DOI Creative Commons
Mitzi M. Gonzales, Valentina R. Garbarino, Erin Pollet

et al.

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(10)

Published: May 15, 2022

Alzheimer's disease and related dementias (ADRD) are among the top contributors to disability mortality in later life. As with many chronic conditions, aging is single most influential factor development of ADRD. Even older adults who remain free dementia throughout their lives, cognitive decline neurodegenerative changes appreciable advancing age, suggesting shared pathophysiological mechanisms. In this Review, we provide an overview cognition, brain morphology, neuropathological protein accumulation across lifespan humans, complementary mechanistic evidence from animal models. Next, highlight selected processes that differentially regulated disease, including aberrant autophagy, mitochondrial dysfunction, cellular senescence, epigenetic changes, cerebrovascular inflammation, lipid dysregulation. We summarize research clinical translational studies link biological underlying ADRD pathogenesis. Targeting fundamental may represent a yet relatively unexplored avenue attenuate both age-related Collaboration fields geroscience neuroscience, coupled new models more closely align human processes, necessary advance novel therapeutic discovery realm.

Language: Английский

Citations

185
Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis DOI Creative Commons
Baiyu Qiu, Fereshteh Zandkarimi,

Carla T. Bezjian

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(5), P. 1177 - 1190.e18

Published: Feb. 1, 2024

Language: Английский

Citations

109
Developing dietary interventions as therapy for cancer DOI
Samuel Taylor,

John N. Falcone,

Lewis C. Cantley

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(8), P. 452 - 466

Published: May 25, 2022

Language: Английский

Citations

95
Axonal energy metabolism, and the effects in aging and neurodegenerative diseases DOI Creative Commons
Sen Yang, Jung Hyun Park, Hui‐Chen Lu

et al.

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: July 20, 2023

Abstract Human studies consistently identify bioenergetic maladaptations in brains upon aging and neurodegenerative disorders of (NDAs), such as Alzheimer’s disease, Parkinson’s Huntington’s Amyotrophic lateral sclerosis. Glucose is the major brain fuel glucose hypometabolism has been observed regions vulnerable to NDAs. Many susceptible are topological central hub connectome, linked by densely interconnected long-range axons. Axons, key components have high metabolic needs support neurotransmission other essential activities. Long-range axons particularly injury, neurotoxin exposure, protein stress, lysosomal dysfunction, etc. Axonopathy often an early sign neurodegeneration. Recent ascribe axonal maintenance failures local dysregulation. With this review, we aim stimulate research exploring metabolically oriented neuroprotection strategies enhance or normalize bioenergetics NDA models. Here start summarizing evidence from human patients animal models reveal correlation between connectomic disintegration aging/NDAs. To encourage mechanistic investigations on how dysregulation occurs during aging/NDAs, first review current literature distinct subdomains: axon initial segments, myelinated arbors harboring pre-synaptic boutons. In each subdomain, focus organization, activity-dependent regulation system, external glial support. Second, mechanisms regulating nicotinamide adenine dinucleotide (NAD + ) homeostasis, molecule for energy metabolism processes, including NAD biosynthetic, recycling, consuming pathways. Third, highlight innate vulnerability connectome discuss its perturbation As deficits developing into NDAs, especially asymptomatic phase, they likely exaggerated further impaired energetic cost neural network hyperactivity, pathology. Future interrogating causal relationship vulnerability, axonopathy, amyloid/tau pathology, cognitive decline will provide fundamental knowledge therapeutic interventions.

Language: Английский

Citations

49
Optimization of Mobile Phase Modifiers for Fast LC-MS-Based Untargeted Metabolomics and Lipidomics DOI Open Access
Tomáš Čajka,

Jiří Hričko,

Lucie Kulhavá

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1987 - 1987

Published: Jan. 19, 2023

Liquid chromatography-mass spectrometry (LC-MS) is the method of choice for untargeted profiling biological samples. A multiplatform LC-MS-based approach needed to screen polar metabolites and lipids comprehensively. Different mobile phase modifiers were tested improve electrospray ionization process during metabolomic lipidomic profiling. For metabolites, hydrophilic interaction LC using a with 10 mM ammonium formate/0.125% formic acid provided best performance amino acids, biogenic amines, sugars, nucleotides, acylcarnitines, sugar phosphate, while reversed-phase (RPLC) 0.1% outperformed organic acids. lipids, RPLC formate or permitted high signal intensity various lipid classes ionized in ESI(+) robust retention times. ESI(-), acetate acetic represented reasonable compromise regarding detected stability times compared alone 0.02% acid. Collectively, we show that methods should be evaluated not only on total number features but also based common by specific platform along long-term

Language: Английский

Citations

45
Multiscale biochemical mapping of the brain through deep-learning-enhanced high-throughput mass spectrometry DOI Creative Commons
Yuxuan Richard Xie, Daniel C. Castro, Stanislav S. Rubakhin

et al.

Nature Methods, Journal Year: 2024, Volume and Issue: 21(3), P. 521 - 530

Published: Feb. 16, 2024

Abstract Spatial omics technologies can reveal the molecular intricacy of brain. While mass spectrometry imaging (MSI) provides spatial localization compounds, comprehensive biochemical profiling at a brain-wide scale in three dimensions by MSI with single-cell resolution has not been achieved. We demonstrate complementary and mapping using MEISTER, an integrative experimental computational (MS) framework. Our framework integrates deep-learning-based reconstruction that accelerates high-mass-resolving MS 15-fold, multimodal registration creating three-dimensional (3D) distributions data integration method fitting cell-specific spectra to 3D datasets. imaged detailed lipid profiles tissues millions pixels large populations acquired from rat identified region-specific contents localizations lipids depending on both cell subpopulations anatomical origins cells. workflow establishes blueprint for future development multiscale characterization

Language: Английский

Citations

28
Lipidome atlas of the adult human brain DOI Creative Commons
Maria Osetrova, Anna Tkachev,

Waltraud Mair

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 25, 2024

Abstract Lipids are the most abundant but poorly explored components of human brain. Here, we present a lipidome map brain comprising 75 regions, including 52 neocortical ones. The composition varies greatly among affecting 93% 419 analyzed lipids. These differences reflect brain’s structural characteristics, such as myelin content (345 lipids) and cell type (353 lipids), also functional traits: connectivity (76 information processing hierarchy (60 lipids). Combining lipid mRNA expression data further enhances association. Biochemically, lipids linked with features display distinct class distribution, unsaturation extent, prevalence omega-3 omega-6 fatty acid residues. We verified our conclusions by parallel analysis three adult macaque brains, targeted 216 lipids, mass spectrometry imaging, assessment sorted murine neurons.

Language: Английский

Citations

26
A lipidome landscape of aging in mice DOI
Hiroshi Tsugawa, Tomoaki Ishihara,

Kota Ogasa

et al.

Nature Aging, Journal Year: 2024, Volume and Issue: 4(5), P. 709 - 726

Published: April 12, 2024

Language: Английский

Citations

21