Ageing research reviews最新文献

The trillions of microbial populations residing in the gut have recently shown that they can be used as a remedy for various diseases. The gut microbiota-brain-axis interface is one unique pathway that the microbiota demonstrates its medicinal value. This medicinal value is further seen when there is a decline in gut microbial diversity (dysbiosis). Dysbiosis leads to neurodegenerative disorders (NDDs). The objective of this review is to ascertain the clinical significance of gut microbiota induced therapeutic strategies. While navigating this important area of interest, we will elucidate the research gaps, the prospects and the potential reverse interventions of the studied NDDs. In addition to our previous work, relevant literature published in English were searched and retrieved from the PubMed database. The 'gut microbiota and Neurodegenerative disorders' were used as keywords during the search period. The Filters applied are: Abstract, Full text, Meta-Analysis, Randomized Controlled Trial, Reviews, in the last 5 years. The articles were analyzed in our unrelenting quest to make sense of the prospects and research gap in gut microbiota-brain-axis. This chapter is a result of this meticulous work. More convincing data from researches on gut microbiota-brain-axis are required to provide clinical significance including neuroimaging studies. Addressing the structural (pathological footprints) and the functional changes (diseases manifestation) involving gut microbiota-brain-axis require a holistic approach. While the pharmacological therapies such as chemotherapeutic and chemobiotic treatment approaches come with low success rates, non-pharmacological interventions are found to be more useful in reversing NDDs. The inability to detect NDDs at an early stage in their clinical history, makes preventive medicinal approaches the must needed and best intervention strategy. Gut-driven treatments have a lot to offer in the management of refractory neurologic diseases.

Background: While the digital-based interventions targeting older adults to prevent age-related health problems such as sarcopenia have grown rapidly in recent years, there are no meta-analyses indicating synthesized pooled estimates.

Objective: To examine the effects of digital-based interventions on sarcopenia-related measures, including physical performance and muscle mass, in healthy community-dwelling older adults.

Methods: Systematic searches were performed on MEDLINE, Web of Science, and Cochrane Library for eligible studies published up to 31 March 2023. The mean difference with a 95 % confidence interval was calculated. Methodological quality was assessed using Cochrane RoB 2.0. The GRADE criteria were used to assess evidence certainty.

Results: Thirteen randomized controlled trials with 742 participants were included in the meta-analysis. Handgrip strength, usual walking speed, five times sit-to-stand performance, and 30-second chair stand test showed significant enhancements with the digital-based interventions. However, there were no significant effects of digital-based interventions in appendicular muscle mass. The overall evidence certainty was low.

Conclusions: Although digital-based interventions for healthy older adults are effective in improving physical functions, evidence certainty is low. Additional randomized controlled trials are thus required to further validate the findings.

Efforts to reduce preventable medication-related harm through medication reviews have increased, but interventions often yield null-results regarding clinical outcomes. We conducted a systematic literature search in four data bases and summarised the available evidence from randomised controlled trials (RCTs) comparing medication reviews and usual care in hospitalised patients regarding hospital readmissions and all-cause mortality by random-effects meta-analyses. Effect size differences by methodological study differences were of special interest. The meta-analysis of all 24 trials on hospital readmissions, including 12,539 participants, showed a statistically significant 8 % decrease in hospital readmissions (risk ratio (RR) [95 % confidence interval]: (0.92 [0.88-0.97], p = 0.002). The number of patient contacts was the most prominent effect modifier in meta-regression (p = 0.003) and the effect of medication reviews was approximately twice as strong (15 %) in 11 trials with 2 or more patient contacts (0.85 [0.78-0.92], p < 0.001). No statistically significant reduction in all-cause mortality was observed in a meta-analysis of all 22 trials with data for this outcome (0.95 [0.86-1.04], p = 0.24), including 12,350 participants. The method of mortality assessment was identified as an effect modifier by meta-regression (p = 0.01). A meta-analysis of 10 trials with complete mortality ascertainment via registries or primary care data showed a significantly 19 % reduced mortality (0.81 [0.70-0.94], p < 0.01). In conclusion, medication reviews reduce the risk of hospital readmission and might also reduce all-cause mortality. Comprehensive mortality assessment was essential for successful trials. Clinical guidelines should recommend medication reviews with multiple patient contacts, involving pharmacists, either for repeated medication reviews or to improve adherence.

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington disease, pose serious threats to human health, leading to substantial economic burdens on society and families. Despite extensive research, the underlying mechanisms driving these diseases remain incompletely understood, impeding effective diagnosis and treatment. In recent years, growing evidence has highlighted the crucial role of oxidative stress in the pathogenesis of various neurodegenerative diseases. However, there is still a lack of comprehensive reviews that systematically summarize the impact of mitochondrial oxidative stress on neurodegenerative diseases. This review aims to address this gap by summarizing the molecular mechanisms by which mitochondrial oxidative stress promotes the initiation and progression of neurodegenerative disorders. Furthermore, it discusses the potential of antioxidant-based therapeutic strategies for the treatment of these diseases. By shedding light on the role of mitochondrial oxidative stress in neurodegenerative diseases, this review not only serves as a valuable reference for further research on the disease mechanisms, but also offers novel perspectives for the treatment of these disorders.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which there is slow and gradual impairment of mental function. Considering the increase in cases due to population aging, the potential benefits of physical training in AD are of great importance and need further elucidation. This study aims to identify the impact of physical training on crucial aspects of AD such as cognitive status, physical performances, quality of life and activities of daily living. The bibliographic research was conducted according to the guidelines outlined in PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). After the selection process, 26 studies were included in the systematic review and meta-analysis. Physical training for up to 12 weeks had a moderate effect on the cognitive status (SMD: 0.34; 95 % CI: 0.07-0.61; p = 0.016), the physical performance (SMD: 0.75; 95 % CI: 0.43-1.06; p = 0.000) and the quality of life (SMD: 0.40; 95 % CI: 0.17-0.63; p = 0.567) of patients with AD, but did not affect their daily living activities (SMD: -0.10; 95 % CI: -0.31-0.12; p = 0.621). Physical training lasting from 16 to 24 weeks had a moderate effect only on the physical performance (SMD: 0.51; 95 % CI: 0.23-0.79; p = 0.000) of patients. Physical training for up to 12 weeks already leads to gains on the cognition, the physical performance and the quality of life of individuals with AD. Beyond the available evidence on health promotion resulting from physical training, guidelines should be established to define ideal training loads for patients with AD. Specific practical recommendations concerning the types, frequency, intensity or duration of physical exercise that may be the most efficient for ameliorating cognition, physical performance and quality of life of individuals with AD are still unclear.

Accumulating evidence suggests that gut microbiota (GM) plays a crucial role in Alzheimer's disease (AD) pathogenesis and progression. This narrative review explores the complex interplay between GM, the immune system, and the central nervous system in AD. We discuss mechanisms through which GM dysbiosis can compromise intestinal barrier integrity, enabling pro-inflammatory molecules and metabolites to enter systemic circulation and the brain, potentially contributing to AD hallmarks. Additionally, we examine other pathophysiological mechanisms by which GM may influence AD risk, including the production of short-chain fatty acids, secondary bile acids, and tryptophan metabolites. The role of the vagus nerve in gut-brain communication is also addressed. We highlight potential therapeutic implications of targeting GM in AD, focusing on antibiotics, probiotics, prebiotics, postbiotics, phytochemicals, and fecal microbiota transplantation. While preclinical studies showed promise, clinical evidence remains limited and inconsistent. We critically assess clinical trials, emphasizing challenges in translating GM-based therapies to AD patients. The reviewed evidence underscores the need for further research to elucidate precise molecular mechanisms linking GM to AD and determine whether GM dysbiosis is a contributing factor or consequence of AD pathology. Future studies should focus on large-scale clinical trials to validate GM-based interventions' efficacy and safety in AD.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by both motor and cognitive impairments. A significant challenge in managing PD is the variability of symptoms and disease progression rates. This variability is primarily attributed to unclear biomarkers associated with the disease and the lack of early diagnostic technologies and effective imaging methods. PD-specific biomarkers are essential for developing practical tools that facilitate accurate diagnosis, patient stratification, and monitoring of disease progression. Hence, creating valuable tools for detecting and diagnosing PD based on specific biomarkers is imperative. Blood testing, less invasive than obtaining cerebrospinal fluid through a lumbar puncture, is an ideal source for these biomarkers. Although such biomarkers were previously lacking, recent advancements in various detection techniques related to PD biomarkers and new imaging methods have emerged. However, basic research requires more detailed guidelines on effectively implementing these biomarkers in diagnostic procedures to enhance the diagnostic accuracy of PD blood testing in clinical practice. This review discusses the developmental trends of PD-related blood biomarker detection technologies, including optical analysis platforms. Despite the progress in developing various biomarkers for PD, their specificity and sensitivity remain suboptimal. Therefore, the integration of multimodal biomarkers along with optical and imaging technologies is likely to significantly improve diagnostic accuracy and facilitate the implementation of personalized medicine. This review forms valid research hypotheses for PD research and guides future empirical studies.

Cellular senescence, a complex biological process resulting in permanent cell-cycle arrest, is central to aging and age-related diseases. A key concept in understanding cellular senescence is the Hayflick Limit, which refers to the limited capacity of normal human cells to divide, after which they become senescent. Senescent cells (SC) accumulate with age, releasing pro-inflammatory and tissue-remodeling factors collectively known as the senescence-associated secretory phenotype (SASP). The causes of senescence are multifaceted, including telomere attrition, oxidative stress, and genotoxic damage, and they extend to influences from microbial sources. Research increasingly emphasizes the role of the microbiome, especially gut microbiota (GM), in modulating host senescence processes. Beneficial microbial metabolites, such as short-chain fatty acids (SCFAs), support host health by maintaining antioxidant defenses and reducing inflammation, potentially mitigating senescence onset. Conversely, pathogenic bacteria like Pseudomonas aeruginosa and Helicobacter pylori introduce factors that damage host DNA or increase ROS, accelerating senescence via pathways such as NF-κB and p53-p21. This review explores the impact of bacterial factors on cellular senescence, highlighting the role of specific bacterial toxins in promoting senescence. Additionally, it discusses how dysbiosis and the loss of beneficial microbial species further contribute to age-related cellular deterioration. Modulating the gut microbiome to delay cellular senescence opens a path toward targeted anti-aging strategies. This work underscores the need for deeper investigation into microbial influence on aging, supporting innovative interventions to manage and potentially reverse cellular senescence.

Neurodegenerative diseases (NDs) are debilitating disorders characterized by the progressive and selective loss of function or structure in the brain and spinal cord. Both chronic and acute forms of these diseases are associated with significant morbidity and mortality, as they involve the degeneration of neurons in various brain regions. Misfolding and aggregation of amyloid proteins into oligomer and β-sheet rich fibrils share as common hallmark and lead to neurotoxicity. Unfortunately, effective curative therapies remain limited, underscoring the urgent need for early diagnosis and differentiation among disorders with overlapping symptoms to guide optimal clinical treatment strategies. Lack of selective probes for detecting soluble amyloid β-oligomer and insoluble amyloid deposits, for example, amyloid β1-42, α-synuclein or Tau proteins, promotes the onset of disease. A variety of sensors are being developed using the Förster resonance transfer mechanism (FRET) effect. However, its efficacy depends on fluorophore donors. Dyes also suffer several drawbacks, including photobleaching, interference from the aggregates, overlapping and blinking effects. Upconversion nanoparticles (UCNPs) solve such issues by acting as alternative fluorescence donors and helping in treating and diagnosing NDs at early stages. In this article, we present the theranostic potential of UCNPs and their critical challenges, along with the future direction. We begin with upconversion sensing mechanism followed with different biomarker detection of NDs using upconversion approach.

Sirtuin-3 (SIRT3) in mitochondria has nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase activity. As such, SIRT3 is crucial in cardiovascular and neurodegenerative diseases. Advanced proteomics and transcriptomics studies have revealed that SIRT3 expression becomes altered when the heart or brain is affected by external stimuli or disease, such as diabetic cardiomyopathy, atherosclerosis, myocardial infarction, Alzheimer's disease, Huntington's disease, and Parkinson's disease. More specifically, SIRT3 participates in the development of these disorders through its deacetylase activity and in combination with downstream signaling pathways. The paper reviews SIRT3's expression changes, roles, and mechanisms associated with the development of cardiovascular and neurodegenerative diseases. Additionally, strategies targeting SIRT3 to treat or regulate cardiovascular and neurodegenerative disease development are discussed.