Ageing research reviews最新文献

Sarcopenia is associated with poor prognosis and mortality following injury. This systematic review and meta-analysis aimed to analyze diagnostic criteria for sarcopenia, as well as to assess its prevalence and impact on health outcomes among trauma patients. We conducted a literature search on MEDLINE, EMBASE, and the Cochrane Library from inception to June 2023. A total of 27 studies were included, involving 8692 individuals (55.5 % men) with a mean age ranging from 42.2 to 80.5 years. The pooled prevalence of sarcopenia in trauma patients was 36.0 % [95 % confidence interval (CI): 29.1-43.0 %, I² = 97.8 %], with a 39.3 % prevalence (95 % CI: 31.0-48.5 %, I² = 96.8 %) in men and a 39.0 % prevalence (95 % CI: 31.4-46.2 %, I² = 94.4 %) in women. Trauma patients with sarcopenia were more prone to complications [risk ratio (RR): 1.16, 95 % CI: 1.03-1.31, I² = 45.8 %] and less able to discharge independently (RR: 0.74, 95 % CI: 0.63-0.86, I² = 33.3 %). The risk of death in trauma patients with sarcopenia was higher than in non-sarcopenic patients [hazard ratio (HR): 1.64, 95 % CI: 1.31-2.04]. Sarcopenia is commonly present in trauma patients and has a negative impact on prognosis. Early assessment and interventions for sarcopenia should be conducted in trauma patients.

Tauopathies encompass a group of approximately 20 neurodegenerative diseases characterized by the accumulation of the microtubule-associated protein tau in brain neurons. The pathogenesis of intracellular neurofibrillary tangles, a hallmark of tauopathies, is initiated by hyperphosphorylated tau protein isoforms that cause neuronal death and lead to diseases like Alzheimer's, Parkinson's disease, frontotemporal dementia, and other complex neurodegenerative diseases. Current applications of tau biomarkers, including imaging, cerebrospinal fluid, and blood-based assays, assist in the evaluation and diagnosis of tauopathies. Emerging research is uncovering various potential strategies to prevent cellular toxicity caused by tau aggregation: 1) suppressing toxic tau aggregation, 2) preventing post-translational modifications of tau, 3) stabilizing microtubules and 4) designing tau-directed immunogens. This review aims to discuss the role of tau in tauopathies along with neuropathological features of the different tauopathies and the new developments in treating tau aggregation with the therapeutics for treating and possibly preventing tauopathies.

Glial cell polarization plays a pivotal role in various neurological disorders. In response to distinct stimuli, glial cells undergo polarization to either mitigate neurotoxicity or facilitate neural repair following injury, underscoring the importance of glial phenotypic polarization in modulating central nervous system function. This review presents an overview of glial cell polarization, focusing on astrocytes and microglia. It explores the involvement of glial polarization in neurological diseases such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, traumatic brain injury, amyotrophic lateral sclerosis, multiple sclerosis and meningoencephalitis. Specifically, it emphasizes the role of glial cell polarization in disease pathogenesis through mechanisms including neuroinflammation, neurodegeneration, calcium signaling dysregulation, synaptic dysfunction and immune response. Additionally, it summarizes various therapeutic strategies including pharmacological treatments, dietary supplements and cell-based therapies, aimed at modulating glial cell polarization to ameliorate brain dysfunction. Future research focused on the spatio-temporal manipulation of glial polarization holds promise for advancing precision diagnosis and treatment of neurological diseases.

This concise review provides new perspectives on systemic reduction of tissue aging by comparing different strategies, such as heterochronic parabiosis, injections of young blood plasma, neutral blood exchange (NBE) and therapeutic plasma exchange (TPE). Unlike previous literature that primarily discusses the need for young blood factors, we emphasize the potential of diluting age-elevated proteins as the way to re-calibrate systemic proteome to its younger state without donor blood. Furthermore, we introduce modulation of proteome noise, as an important part of understanding tissue aging and as a critical mechanism for tissue rejuvenation. We discuss studies on the dominance of aged systemic milieu in promoting progeric phenotypes in young cells, in vitro, and in multiple tissues of young animals, in vivo. We support our arguments with evidence showing a significant age-related increase in protein synthesis, in noise of newly synthesized proteomes, and in the rapid induction of these aging phenotypes in young muscle by exposure to aged tissue. We summarize the significance of these findings for future research on aging and longevity.

This review provides an in-depth analysis of the complex role of alpha-synuclein (α-Syn) in the development of α-synucleinopathies, with a particular focus on its structural diversity and the resulting clinical variability. The ability of α-Syn to form different strains or polymorphs and undergo various post-translational modifications significantly contributes to the wide range of symptoms observed in disorders such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), as well as in lesser-known non-classical α-synucleinopathies. The interaction between genetic predispositions and environmental factors further complicates α-synucleinopathic disease pathogenesis, influencing the disease-specific onset and progression. Despite their common pathological hallmark of α-Syn accumulation, the clinical presentation and progression of α-synucleinopathies differ significantly, posing challenges for diagnosis and treatment. The intricacies of α-Syn pathology highlight the critical need for a deeper understanding of its biological functions and interactions within the neuronal environment to develop targeted therapeutic strategies. The precise point at which α-Syn aggregation transitions from being a byproduct of initial disease triggers to an active and independent driver of disease progression - through the propagation and acceleration of pathogenic processes - remains unclear. By examining the role of α-Syn across various contexts, we illuminate its dual role as both a marker and a mediator of disease, offering insights that could lead to innovative approaches for managing α-synucleinopathies.

Alzheimer's disease (AD) is a progressive, degenerative disorder of the central nervous system. Despite extensive research conducted on this disorder, its precise pathogenesis remains unclear. In recent years, the microbiota-gut-brain axis has attracted considerable attention within the field of AD. The gut microbiota communicates bidirectionally with the central nervous system through the gut-brain axis, and alterations in its structure and function can influence the progression of AD. Consequently, regulating the gut microbiota to mitigate the progression of AD has emerged as a novel therapeutic approach. Currently, numerous studies concentrate on the intrinsic relationship between the microbiota-gut-brain axis and AD. In this paper, we summarize the multifaceted role of the gut microbiota in AD and present detailed therapeutic strategies targeting the gut microbiota, including the treatment of AD with Traditional Chinese Medicine (TCM), which has garnered increasing attention in recent years. Finally, we discuss potential therapeutic strategies for modulating the gut microbiota to alleviate the progression of AD, the current challenges in this area of research, and provide an outlook on future research directions in this field.

Over the past several decades, high-resolution brain imaging, blood and cerebrospinal fluid analyses, and other advanced technologies have changed diagnosis from an exercise depending primarily on the history and physical examination to a computer- and online resource-aided process that relies on larger and larger quantities of data. In addition, randomized controlled trials (RCT) at a population level have led to many new drugs and devices to treat neurological disease, including disease-modifying therapies. We are now at a crossroads. Combinatorially profound increases in data about individuals has led to an alternative to population-based RCTs. Genotyping and comprehensive "deep" phenotyping can sort individuals into smaller groups, enabling precise medical decisions at a personal level. In neurology, precision medicine that includes prediction, prevention and personalization requires that genomic and phenomic information further incorporate imaging and behavioral data. In this article, we review the genomic, phenomic, and computational aspects of precision medicine for neurology. After defining biological markers, we discuss some applications of these "-omic" and neuroimaging measures, and then outline the role of computation and ultimately brain simulation. We conclude the article with a discussion of the relation between precision medicine and value-based care.

Dementia affects millions of people worldwide. Since effective treatments are still lacking, it is important to identify factors that may help prevent dementia. Recent studies suggest environmental factors may affect dementia risk, but findings are inconsistent and often rely on subjective measures. This study evaluated the association between objectively measured environmental factors, such as air pollution and built environment features, and the risk of dementia and cognitive decline. We systematically reviewed studies that employed objective measures of environmental factors and reported their association with dementia risk and cognitive decline. Meta-analysis was performed to synthesize data on environmental exposures and the onset of dementia. Air pollution exposure was linked to higher dementia risk (PMx risk ratio 1.09; 95 % CI 1.06,1.12) (NOx risk ratio 1.10; 95 % CI 1.01,1.20) and cognitive decline, while exposure to park areas or green/blue spaces was generally associated with reduced dementia risk (risk ratio 0.94; 95 % CI 0.92,0.96) and slower cognitive decline. Living closer to major roads increased the risk of dementia (risk ratio 1.10; 95 % CI 1.06,1.13), and cognitive impairment. Street layouts with better connectivity and walkability are associated with a reduced risk of cognitive impairment. Access to local amenities, such as food stores, community centers, and healthcare amenities, supports cognitive health. These findings underscore the importance of considering environmental factors in dementia prevention and highlight the need for further research to clarify the role of urban design in supporting cognitive health.

Scopolamine, widely regarded as the gold standard in preclinical studies of memory impairments, acts as a non-selective antagonist of central and peripheral muscarinic receptors. While its application in modeling dementia primarily involves antagonism at the M₁ receptor, its non-selective peripheral actions may introduce adverse effects that influence behavioral test outcomes. This review analyzes preclinical findings to consolidate knowledge on scopolamine's use and elucidate potential mechanisms responsible for its amnestic effects. We focused on recognition, spatial, and emotional memory processes, alongside executive functions such as attention, cognitive flexibility, and working memory. The cognitive effects of scopolamine are highly dose-dependent, influenced by factors such as species, age, and sex of subjects. Notably, scopolamine rapidly induces observable memory impairments across species, from fish to rodents and primates, often with deficits that can persist for days. However, the compound's broad action on muscarinic receptors and its peripheral side effects, including pupil dilation and reduced salivation, complicates result interpretation, particularly in tasks requiring visual discrimination or food intake. The review also highlights scopolamine's translational value in modeling dementia and Alzheimer's disease, emphasizing the importance of considering individual factors and task-specific designs. Despite its widespread use, scopolamine's limited specificity for cholinergic dysfunction and inability to fully mimic the complex pathophysiology of cognitive disorders like Alzheimer's and Parkinson's disease point to the need for complementary models. This review aims to guide researchers in using scopolamine for modeling cognitive impairments, ensuring attention to factors impacting experimental outcomes.

The central nervous system (CNS) is wired by a complex network of integrated glial and neuronal signals, which is critical for its development and homeostasis. In this context, glia-glia communication is a complex and dynamic process that is essential for ensuring optimal CNS function. Semaphorins, which include secreted and transmembrane molecules, and their receptors, mainly found in the plexin and neuropilin families, are expressed in a wide range of cell types, including glia. In the CNS, semaphorin signalling is involved in a spectrum of processes, including neurogenesis, neuronal migration and wiring, and glial cell recruitment. Recently, semaphorins and plexins have attracted intense research aimed at elucidating their roles in instructing glial cell behavior during development or in response to inflammatory stimuli. In this review, we provide an overview of the multifaceted role of semaphorins in glia-glia communication, highlighting recent discoveries about semaphoring-dependent regulation of glia functions in healthy conditions. We also discuss the mechanisms of gliaglia crosstalk mediated by semaphorins under pathological conditions, and how these interactions may provide potential avenues for therapeutic intervention in neuroinflammation-mediated neurodegeneration.