Chi3l1 /YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer’s disease pathogenesis

Science Translational Medicine, Journal Year: 2020, Volume and Issue: 12(574)

Published: Dec. 16, 2020

Regulation of glial activation and neuroinflammation are critical factors in the pathogenesis Alzheimer's disease (AD). YKL-40, a primarily astrocytic protein encoded by gene Chi3l1, is widely studied cerebrospinal fluid biomarker that increases with aging early AD. However, function Chi3l1/YKL-40 AD unknown. In cohort patients AD, we observed variant human CHI3L1 gene, which results decreased CSF YKL-40 expression, was associated slower progression. At baseline, Chi3l1 deletion mice had no effect on astrocyte while modestly promoting microglial activation. mouse APP/PS1 model amyloid plaque burden increased periplaque expression lysosomal marker CD68, suggesting may suppress phagocytic promote accumulation. Accordingly, knockdown phagocytosis zymosan particles β-amyloid peptide both astrocytes microglia vitro. We further regulated circadian clock, as core clock proteins BMAL1 or CLOCK/NPAS2 strongly suppresses basal whereas negative regulators PER1/PER2 expression. Basal mRNA nonrhythmic because long half-life astrocytes. inflammatory induction gated clock. Our findings reveal modulator humans suggest regulates induction.

Language: Английский

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Relationship Between Sarcopenia and Cardiovascular Diseases in the Elderly: An Overview

Frontiers in Cardiovascular Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Dec. 9, 2021

With the advent of population aging, aging-related diseases have become a challenge for governments worldwide. Sarcopenia has defined as clinical syndrome associated with age-related loss such skeletal muscle mass, strength, function, and physical performance. It is commonly seen in elderly patients chronic diseases. Changes lean mass are common critical determinants pathophysiology progression cardiovascular (CVDs). may be one most important causes poor function decreased cardiopulmonary CVDs. induce CVDs through pathogenic pathways malnutrition, inactivity, insulin resistance, inflammation; these mechanisms interact. In this study, we aimed to investigate relationship between sarcopenia elderly. Further research urgently needed understand better relationship, pathophysiology, presentation, diagnostic criteria, CVDs, which shed light on potential interventions improve outcomes provide greater insight into disorders above.

Language: Английский

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Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Language: Английский

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Associations of sleep disorders with all-cause MCI/dementia and different types of dementia – clinical evidence, potential pathomechanisms and treatment options: A narrative review

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 22, 2024

Due to worldwide demographic change, the number of older persons in population is increasing. Aging accompanied by changes sleep structure, deposition beta-amyloid (Aß) and tau proteins vascular can turn into mild cognitive impairment (MCI) as well dementia. Sleep disorders are discussed both a risk factor for consequence MCI/dementia. Cross-sectional longitudinal population-based case–control studies revealed disorders, especially sleep-disorderded breathing (SDB) excessive or insufficient durations, factors all-cause Regarding different dementia types, SDB was associated with while insomnia/insufficient related an increased Alzheimer’s disease (AD). Scarce still inconsistent evidence suggests that therapy continuous positive airway pressure (CPAP) SDB, improve cognition patients without comorbid delay onset MCI/dementia previous impairment. potential pathomechanisms via which lead MCI/dementia, disturbed sleep, chronic deficit impair glymphatic clearance amyloid aggregation resulting brain structures responsible cognition. Orexins modulate Aß pathology. Their diurnal fluctuation suppressed fragmentation expression at point hippocampal atrophy, contributing progression Additionally, profile such inflammation, endothelial dysfunction atherosclerosis foster neurodegenerative There ample indicating structure aging also disorder Therefore, should be identified treated early.

Language: Английский

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Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration

Sleep and Vigilance, Journal Year: 2020, Volume and Issue: 4(2), P. 81 - 87

Published: Sept. 26, 2020

Language: Английский

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Defining circadian disruption in neurodegenerative disorders

Journal of Clinical Investigation, Journal Year: 2021, Volume and Issue: 131(19)

Published: Sept. 30, 2021

Neurodegenerative diseases encompass a large group of conditions that are clinically and pathologically diverse yet linked by shared pathology misfolded proteins. The accumulation insoluble aggregates is accompanied progressive loss vulnerable neurons. For some patients, the symptoms motor focused (ataxias), while others experience cognitive psychiatric (dementias). Among neurodegenerative disruption sleep/wake cycle occurs early in trajectory disease may be risk factor for development. In many cases, timing sleep other rhythmic physiological markers immediately raises possibility neurodegeneration-driven circadian system. aim this Review to summarize evidence supporting hypothesis core symptom within diseases, including Alzheimer's disease, Huntington's Parkinson's discuss latest progress field. discusses processes disrupt structure function system describes circadian-based interventions as well timed drug treatments improve wide range associated with disorders. It also identifies key gaps our knowledge.

Language: Английский

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A Growing Link between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(1), P. 504 - 504

Published: Jan. 3, 2022

Type 2 diabetes mellitus (T2DM) patients are at a higher risk of developing Alzheimer’s disease (AD). Mounting evidence suggests the emerging important role circadian rhythms in many diseases. Circadian rhythm disruption is considered to contribute both T2DM and AD. Here, we review relationship among disruption, AD, suggest that occurrence progression AD may part be associated with disruption. Then, summarize promising therapeutic strategies targeting dysfunction for including pharmacological treatment such as melatonin, orexin, molecules, well non-pharmacological treatments like light therapy, feeding behavior, exercise.

Language: Английский

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Circadian rhythms, gut microbiota, and diet: Possible implications for health

Nutrition Metabolism and Cardiovascular Diseases, Journal Year: 2023, Volume and Issue: 33(8), P. 1490 - 1500

Published: May 15, 2023

Over the past years, interest in chrono-nutrition has grown enormously as fundamental role of circadian rhythms regulating most physiological and metabolic processes become clearer. Recently, influence on gut microbiota (GM) composition also emerged, more than half total microbial fluctuates rhythmically throughout day. At same time, other studies have observed that GM itself synchronises host's biological clock through signals a different nature. Therefore, it been hypothesised there is two-way communication between host GM, but researchers only just begun to identify some its action mechanisms. The manuscript aim is, therefore, gather combine latest evidence field with recent research order investigate their relationship potential impact human health.Considering current evidence, desynchronization closely associated an alteration abundance functionality consequent deleterious effects health, such increased risk numerous pathologies, including cardiovascular disease, cancer, irritable bowel depression. A key maintaining balance seems be attributed meal-timing diet quality, well certain metabolites, particular short-chain fatty acids.Future are needed decipher link specific patterns relation disease frameworks.

Language: Английский

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Dysfunction of circadian and sleep rhythms in the early stages of Alzheimer's disease

Acta Physiologica, Journal Year: 2023, Volume and Issue: 238(2)

Published: March 31, 2023

Abstract Dysfunction of circadian and sleep rhythms is an early feature many neurodegenerative diseases. Alzheimer's disease (AD) a progressive disorder resulting in cognitive psychiatric disturbances. Although it largely unclear whether dysfunctions contribute to the etiology AD or are consequence disease, there evidence that these conditions involved complex self‐reinforcing bidirectional relationship. According recent studies, dysregulation clock already occurs during asymptomatic stage could promote neurodegeneration. Thus, restoration preclinical may represent opportunity for intervention slow course.

Language: Английский

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Inflammaging and Brain Aging

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(19), P. 10535 - 10535

Published: Sept. 30, 2024

Progress made by the medical community in increasing lifespans comes with costs of incidence and prevalence age-related diseases, neurodegenerative ones included. Aging is associated a series morphological changes at tissue cellular levels brain, as well impairments signaling pathways gene transcription, which lead to synaptic dysfunction cognitive decline. Although we are not able pinpoint exact differences between healthy aging neurodegeneration, research increasingly highlights involvement neuroinflammation chronic systemic inflammation (inflammaging) development age-associated via pathogenic cascades, triggered dysfunctions circadian clock, gut dysbiosis, immunosenescence, or impaired cholinergic signaling. In addition, gender susceptibility course neurodegeneration that appear be mediated glial cells emphasize need for future this area an individualized therapeutic approach. rejuvenation still its very early infancy, accumulated knowledge on various involved promoting senescence opens perspective interfering these preventing delaying senescence.

Language: Английский

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