Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Language: Английский

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

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

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Microbiota-derived metabolites as drivers of gut–brain communication

Gut Microbes, Journal Year: 2022, Volume and Issue: 14(1)

Published: July 28, 2022

Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The microbes transform metabolize dietary- host-derived molecules generating diverse group metabolites local systemic effects. bi-directional communication between brain residing gut, so-called gut–brain axis, consists network immunological, neuronal, endocrine signaling pathways. Although full variety mechanisms crosstalk is yet to be established, existing data demonstrates that single metabolite or its derivatives are likely among key inductors within axis communication. However, more research needed understand molecular underlying how alter functions, examine if different interventional approaches targeting could used prevention treatment neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic ZO Zonula occludens proteins

Language: Английский

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The microbiota–gut–brain axis and neurodevelopmental disorders

Protein & Cell, Journal Year: 2023, Volume and Issue: 14(10), P. 762 - 775

Published: May 11, 2023

Abstract The gut microbiota has been found to interact with the brain through microbiota–gut–brain axis, regulating various physiological processes. In recent years, impacts of on neurodevelopment this axis have increasingly appreciated. is commonly considered regulate three pathways, immune pathway, neuronal and endocrine/systemic overlaps crosstalks in between. Accumulating studies identified role neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity Rett Syndrome. Numerous researchers examined pathophysiological mechanisms influenced by (NDDs). This review aims provide a comprehensive overview advancements research pertaining microbiota-gut-brain NDDs. Furthermore, we analyzed both current state progress discuss future perspectives field.

Language: Английский

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Oxidative stress in Alzheimer’s disease: current knowledge of signaling pathways and therapeutics

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Jan. 2, 2024

Language: Английский

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Aging microglia

Cellular and Molecular Life Sciences, Journal Year: 2023, Volume and Issue: 80(5)

Published: April 21, 2023

Abstract Microglia are the tissue-resident macrophage population of brain, specialized in supporting CNS environment and protecting it from endogenous exogenous insults. Nonetheless, their function declines with age, ways that remain to be fully elucidated. Given critical role played by microglia neurodegenerative diseases, a better understanding aging phenotype is an essential prerequisite designing preventive therapeutic strategies. In this review, we discuss most recent literature on aging, comparing findings rodent models human subjects.

Language: Английский

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The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(20), P. 4491 - 4538

Published: Sept. 27, 2023

The physiological consequences of stress often manifest in the gastrointestinal tract. Traumatic or chronic is associated with widespread maladaptive changes throughout gut, although comparatively little known about effects acute stress. Furthermore, these stress-induced gut may increase susceptibility to disorders and infection, impact critical features neural behavioural response by impairing gut-brain axis communication. Understanding mechanisms behind enteric nervous system circuitry, visceral sensitivity, barrier function, permeability, microbiota following an important research objective pathophysiological implications both neurogastroenterology psychiatry. Moreover, has emerged as a key aspect physiology sensitive In this review, we focus on different aspects tract including function well immune, humoral neuronal elements involved discuss evidence for role disorders. Existing gaps current literature are highlighted, possible avenues future integrated perspective have been suggested. A more complete understanding spatial temporal dynamics host microbial kinds stressors will enable full exploitation diagnostic therapeutic potential fast-evolving field host-microbiome interactions.

Language: Английский

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Cellular senescence in white matter microglia is induced during ageing in mice and exacerbates the neuroinflammatory phenotype

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: June 23, 2023

Cellular senescence, a state of irreversible cell-cycle arrest caused by variety cellular stresses, is critically involved in age-related tissue dysfunction various organs. However, the features cells central nervous system that undergo senescence and their role neural impairment are not well understood as yet. Here, through comprehensive investigations utilising single-cell transcriptome analysis mouse models, we show microglia, particularly white matter, brain spinal cord during ageing disease models involving demyelination. Microglial predominantly detected disease-associated which appear neurodegenerative diseases. We also find commensal bacteria promote accumulation senescent microglia ageing. Furthermore, knockout p16INK4a, key inducer, ameliorates neuroinflammatory phenotype damaged cords mice. These results advance our understanding open up possibilities for treatment disorders.

Language: Английский

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Prebiotic and Probiotic Modulation of the Microbiota–Gut–Brain Axis in Depression

Nutrients, Journal Year: 2023, Volume and Issue: 15(8), P. 1880 - 1880

Published: April 13, 2023

Emerging evidence demonstrates that alterations to the gut microbiota can affect mood, suggesting microbiota–gut–brain (MGB) axis contributes pathogenesis of depression. Many these pathways overlap with way in which are thought contribute metabolic disease progression and obesity. In rodents, prebiotics probiotics have been shown modulate composition function microbiota. Together germ-free rodent models, provided compelling for a causal relationship between microbes, microbial metabolites, altered neurochemical signalling inflammatory brain. humans, probiotic supplementation has demonstrated modest antidepressant effects individuals depressive symptoms, though more studies clinically relevant populations needed. This review critically discusses role MGB depression pathophysiology, integrating preclinical clinical evidence, as well putative routes communication microbiota–gut interface A critical overview current approaches investigating microbiome changes is provided. To effectively translate breakthroughs research into novel therapies, rigorous placebo-controlled trials alongside mechanistic biochemical understanding prebiotic action required from future research.

Language: Английский

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Gut microbiome-targeted therapies for Alzheimer’s disease

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)

Published: Nov. 7, 2023

The advent of high­throughput ‘omics’ technologies has improved our knowledge gut microbiome in human health and disease, including Alzheimer’s disease (AD), a neurodegenerative disorder. Frequent bidirectional communications mutual regulation exist between the gastrointestinal tract central nervous system through gut-brain axis. A large body research reported close association microbiota AD development, restoring healthy may curb or even improve symptoms progression. Thus, modulation become novel paradigm for clinical management AD, emerging effort focused on developing potential strategies preventing and/or treating disease. In this review, we provide an overview connection causal relationship dysbiosis mechanisms driving progression, successes challenges implementing available microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, fecal transplantation) preventive therapeutic preclinical intervention studies AD. Finally, discuss future directions field.

Language: Английский

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