Ageing Research Reviews最新文献

Alzheimer’s disease (AD), the most predominant neurodegenerative disease and a quintessential entity within the dementia umbrella, is a global public health crisis. While the lack of disease modifying therapies has been a weak point in AD treatment, the success of recently approved monoclonal antibody-based therapeutics (aducanumab and lecanemab) targeted at the removal of amyloid-beta (Aβ) peptides in the brain is still under debate. There are multiple safety concerns about these approved neurotherapeutics including amyloid-related imaging abnormalities, stroke, meningitis, encephalitis, and even death. Novel paradigms focused on aquaporin-4-mediated neuro-perivascular Aβ and Tau protein clearance pathway are garnering attention. In this paper, we argue that orchestrating the drug discovery focused on glymphatic clearance-facilitating drugs (“glymphotherapeutics”) might be a potentially novel and viable strategy to mitigate the progression and improve the clinical outcomes of AD.

Aging is generally accompanied by a progressive loss of metabolic homeostasis. Targeting metabolic processes is an attractive strategy for healthy-aging. Numerous natural compounds have demonstrated strong anti-aging effects. This review summarizes recent findings on metabolic pathways involved in aging and explores the anti-aging effects of natural compounds by modulating these pathways. The potential anti-aging effects of natural extracts rich in biologically active compounds are also discussed. Regulating the metabolism of carbohydrates, proteins, lipids, and nicotinamide adenine dinucleotide is an important strategy for delaying aging. Furthermore, phenolic compounds, terpenoids, alkaloids, and nucleotide compounds have shown particularly promising effects on aging, especially with respect to metabolism regulation. Moreover, metabolomics is a valuable tool for uncovering potential targets against aging. Future research should focus on identifying novel natural compounds that regulate human metabolism and should delve deeper into the mechanisms of metabolic regulation using metabolomics methods, aiming to delay aging and extend lifespan.

Background

The prevalence of stroke-related sarcopenia has been noted; however, epidemiological data and interventions that increase or reduce the incidence of stroke-related sarcopenia remain lacking.

Methods

Studies on stroke-related sarcopenia were included in association or interventional analyses. All analyses were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two evaluators independently extracted the data.

Results

Female stroke patients had a higher preference for sarcopenia than male patients (pooled odds ratio [OR] = 0.670, 95 % CI 0.533–0.842, p = 0.001). Although stroke patients without drug use have improved skeletal muscle mass index (SMI) (MD = 0.272, 95 % CI 0.087–0.457, p = 0.004), handgrip strength (HGS) was not significantly altered (MD = −0.068, 95 % CI −0.221–0.076, p = 0.354). Stroke patients with nutrient interventions have improved SMI (MD = −0.354, 95 % CI −0.635- −0.073, p = 0.014) and HGS (MD = −0.394, 95 % CI −0.678- −0.111, p = 0.006); the synergistic effect of rehabilitation exercise has not been ruled out. Whether a sex difference exists in these interventions remains to be investigated. The underlying pathological mechanisms and potential therapeutic strategies for this disease are discussed.

Conclusion

Sex difference, proteostasis, and mitochondrial function may impact the incidence of stroke-related sarcopenia. Understanding the underlying pathological mechanisms and potential therapeutic targets for this disease will provide new insights into disease treatment, prevention, and drug development.

Background

The role of gut bacteria in preventing and delaying osteoporosis has been studied. However, the causal relationship between gut bacteria, plasma proteins, circulating metabolites and osteoporosis (OP) risk has not been fully revealed.

Materials and methods

In this study, a two-sample Mendelian randomization study (MR) approach was used to assess the causal associations between gut bacteria, plasma proteins and circulating metabolites, and osteoporosis risk using Genome Wide Association Study (GWAS) data from gut bacteria(n=8208), plasma proteins(n=2263), circulating metabolites (n=123), and osteoporosis (3203 cases and 16380452 controls). Inverse-variance weighted (IVW) was used as the main analytical method to estimate the MR causal effect and to perform directional sensitivity analysis of causality. Finally, the mediating effect values for the influence of gut flora on OP pathogenesis through circulating metabolites were calculated by univariate MR analysis, and multivariate MR analysis. Next, we evaluated the effect of Phosphatidylcholine on the osteogenic function of bone marrow mesenchymal stem cells (BMSCs) through relevant experiments, including Edu detection of cell proliferation, alkaline phosphatase (ALP) staining, Alizarin red staining to evaluate osteogenic function, qPCR and WB detection of osteogenic differentiation related gene expression.

Results

A total of 9 gut microbial taxa, 15 plasma proteins and eight circulating metabolites were analysed for significant causal associations with the development of OP. Significant causal effects of 7 on gut bacteria, plasma proteins and circulating metabolites were analysed by univariate MR analysis and these results were used as exposure factors for subsequent multivariate MR. Multivariate MR analyses yielded a significant effect of circulating metabolites Phosphatidylcholine and other cholines on OP (P<0.05). Further mediation effect analysis showed that the mediation effect of Bifidobacteriaceae affecting OP through the circulating metabolite Phosphatidylcholine and other cholines was −0.0224, with a 95 % confidence interval for the mediation effect that did not include 0, and the complete mediation effect was significant. Phosphatidylcholine can promote BMSCs proliferation and osteogenesis.

Conclusion

Our study demonstrated significant causal associations of gut bacteria, plasma proteins and circulating metabolites on OP, and that Bifidobacteriaceae affect OP through the circulating metabolites Phosphatidylcholine and other cholines. Phosphatidylcholine affects the osteogenic ability of BMSCs. Further exploration of potential microbiota-associated mechanisms of bone metabolism may offer new avenues for osteoporosis prevention and treatment of osteoporosis.

Lactoferrin (Lf) is a multifunctional protein in the transferrin family. It is involved in many physiological functions, including the regulation of iron absorption and immune response. It also has antibacterial, antiviral, anti-inflammatory, anticancer and antioxidant capabilities under pathophysiological conditions. The mammalian lactoferrin receptor (LfR) plays a key role in mediating multiple functions of Lf. Studies have shown that Lf/LfR is abnormally expressed in the brain of Parkinson's disease, and the excessive accumulation of iron in the brain caused by the overexpression of Lf and LfR is considered to be one of the initial causes of the degeneration of dopaminergic neurons in Parkinson’s disease. On the other hand, a number of recent studies have reported that Lf/LfR has a significant neuroprotective effect on Parkinson’s disease. In other words, it seems paradoxical that Lf/LfR has both neurodegenerative and neuroprotective effects in Parkinson’s disease. This article focuses on recent advances in the possible mechanisms of the neurodegenerative and neuroprotective effects of Lf/LfR in Parkinson’s disease and discusses why Lf/LfR has a seemingly contradictory role in the development of Parkinson’s disease. Based on the evidence obtained so far, we believed that Lf/LfR has a neuroprotective effect on Parkinson's disease, while as to whether the overexpressed Lf/LfR is the cause of the development of Parkinson’s disease, the current evidence is insufficient and further investigation needed.

Heart failure (HF), as the terminal manifestation of multiple cardiovascular diseases, causes a huge socioeconomic burden worldwide. Despite the advances in drugs and medical-assisted devices, the prognosis of HF remains poor. HF is well-accepted as a myriad of subcellular dys-synchrony related to detrimental structural and functional remodelling of cardiac components, including cardiomyocytes, fibroblasts, endothelial cells and macrophages. Through the covalent chemical process, post-translational modifications (PTMs) can coordinate protein functions, such as re-localizing cellular proteins, marking proteins for degradation, inducing interactions with other proteins and tuning enzyme activities, to participate in the progress of HF. Phosphorylation, acetylation, and ubiquitination predominate in the currently reported PTMs. In addition, advanced HF is commonly accompanied by metabolic remodelling including enhanced glycolysis. Thus, glycosylation induced by disturbed energy supply is also important. In this review, firstly, we addressed the main types of HF. Then, considering that PTMs are associated with subcellular locations, we summarized the leading regulation mechanisms in organelles of distinctive cell types of different types of HF, respectively. Subsequently, we outlined the aforementioned four PTMs of key proteins and signaling sites in HF. Finally, we discussed the perspectives of PTMs for potential therapeutic targets in HF.

Neurodegenerative diseases (NDDs) are identified by the progressive deterioration of neurons and a subsequent decline in cognitive function, creating an enormous burden on the healthcare system globally. Neuroinflammation is an intricate procedure that initiates the immune response in the central nervous system (CNS) and significantly impacts the expansion of NDDs. This study scrutinizes the complicated interaction between neuronal degeneration and neuroinflammation, with an appropriate emphasis on their reciprocal impacts. It also describes how neuroinflammatory reactions in NDDs are controlled by activating certain pro-inflammatory transcription factors, including p38 MAPK, FAF1, Toll-like receptors (TLRs), and STAT3. Alternatively, it evaluates the impact of pro-survival transcription factors, such as the SOCS pathway, YY1, SIRT1, and MEF2, which provide neuroprotective protection against damage triggered by neuroinflammation. Moreover, we study the feasibility of accommodating drug repositioning as a therapeutic approach for treating neuroinflammatory disorders. This suggests the use of existing medications for novel utilization in the treatment of NDDs. Furthermore, the study intends to reveal novel biomarkers of neuroinflammation that contribute fundamental observation for the initial detection and diagnosis of these disorders. This study aims to strengthen therapy interference and augment patient outcomes by combining ongoing data and evaluating novel therapeutic and diagnostic approaches. The goal is to devote the growth of an effective strategy to reducing the impact of neuroinflammation on neuronal protection in NDDs.

Enigmatic sarcopenic obesity is still a challenge for science and adds to the global public health burden. The progressive accumulation of body fat combined with a dysfunctional skeletal muscle structure and composition, oxidative stress, mitochondrial dysfunction, and anabolic resistance, among other aggravating factors, together represent the seriousness and complexity of treating the metabolic disorder of sarcobesity in aging. For this reason, further studies are needed that encourage the support of therapeutic management. It is along these lines that we direct the reader to therapeutic approaches that demonstrate important, but still obscure, outcomes in the physiological conditions of sarcobesity, such as the role of taurine in modulating inflammatory and antioxidant mechanisms in muscle and adipose tissue, as well as the management of gut microbiota, able to systemically re-establish the structure and function of the gut-muscle axis, in addition to the merits of physical exercise as an instrument to improve muscular health and lifestyle quality.

Introduction

Recent studies have suggested that sustained multidomain interventions, including physical exercise, may be beneficial in preventing cognitive decline. This review aims to assess the impact of prolonged physical exercise and multidomain strategies on overall cognitive faculties and dementia risk among community-dwelling older adults without dementia.

Methods

We systematically searched PubMed, Web of Science, PsychInfo, and CINHAL databases from inception until April 1, 2024, for randomized controlled trials that investigated the effects of long-term (≥ 12 months) physical exercise or multidomain interventions on non-demented, community-dwelling older adults. The primary outcomes assessed were changes in global cognition and the risk of mild cognitive impairment (MCI) or dementia. Standardized mean differences (SMD) and risk ratios (RR) with 95 % confidence intervals were computed using a random-effects inverse-variance method with the Hartung-Knapp-Sidik-Jonkman adjustment for effect size calculation. The Cochrane Risk-of-Bias-2 tool (RoB-2) was used for bias assessment, and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was applied to evaluate the certainty of evidence.

Results

Sixteen trials, including 11,402 participants (mean age 73.2 [±5.5] years; 62.3 % female) were examined. The risk of bias was low. Moderate-certainty evidence indicated that physical exercise interventions had modest to no effect on cognitive function (k= 9, SMD: 0.05; 95 % CI: −0.04–0.13; p = 0.25), whereas multidomain interventions were significantly impactful (k=7, SMD: 0.09; 95 % CI: 0.04–0.15; p < 0.01). Physical exercise interventions did not alter MCI risk (k= 4, RR: 0.98; 95 % CI: 0.73–1.31; p = 0.79) or dementia onset (k= 4, RR: 0.61; 95 % CI: 0.25–1.52; p = 0.19), with very low-to low-certainty evidence, respectively.

Conclusions

Integrative multidomain strategies incorporating physical exercise may benefit the global cognitive function of older adults. However, long-term physical exercise alone did not yield any cognitive gains. The effectiveness of such exercise interventions to mitigate the overall risk of incident MCI and dementia warrants further research.

Background

Dance represents a promising alternative to traditional physical activity (PA), appealing due to its ease of implementation and its associated health benefits. By incorporating technology-based dance interventions into the development of PA programs, there is potential to significantly increase PA participation and improve fitness levels across diverse population groups. This systematic scoping review and meta-synthesis aimed to investigate the effectiveness of technology-based dance interventions as a means of advancing public health objectives.

Methods

A comprehensive literature review was conducted using various databases ( PubMed, Web of Science, ProQuest, MEDLINE, and SPORTDiscus) to identify pertinent publications. We specifically focused on studies evaluated the impact of technology-based dance interventions on health-related outcomes and PA levels. Methodological quality assessment was carried out using the Cochrane RoB 2 and ROBINS-I tools. Data analysis and theme identification were facilitated using NVivo 14. Additionally, this study was registered on the Open Science Framework at https://osf.io/rynce/registrations.

Results

A total of 3135 items identified through the literature search. Following screening, twelve items met the study’s inclusion criteria, with an additional three articles located through manual searching. These 15 studies examined on three types of technology-based dance intervention: mobile health (mHealth) combination, online /telerehabilitation classes, and exergaming dance programs. The analysis included 344 participants, with mean ages ranging from 15.3 ± 1.2–73.6 ± 2.2 years. There were five population groups across the studies: middle-aged and older adults, individuals with Parkinson’s disease (PD), individuals with stroke, overweight adults, and overweight adolescents. The meta-synthesis revealed three primary themes: Acceptability, Intervention effects, and Technology combinations.

Conclusion

The advantages highlighted in this scoping review and meta-synthesis of technology-based dance interventions indicating that this type of PA could provide an effective solution to the growing issue of physical inactivity. It also presents a promising strategy for systematically improving fitness and health across populations, particularly among older individuals.