Ageing research reviews最新文献

During the last few decades, life expectancy has increased worldwide along with the prevalence of several age-related diseases. Among aging pathways, cellular senescence and chronic inflammation (or "inflammaging") appear to be connected to gut homeostasis and dysbiosis of the microbiome. Cellular senescence is a state of essentially irreversible cell cycle arrest that occurs in response to stress. Although senescent cells (SC) remain metabolically active, they do not proliferate and can secrete inflammatory and other factors comprising the senescence-associated secretory phenotype (SASP). Accumulation of SCs has been linked to onset of several age-related diseases, in the brain, bones, the gastrointestinal tract, and other organs and tissues. The gut microbiome undergoes substantial changes with aging and is tightly interconnected with either successful (healthy) aging or disease. Senotherapeutic drugs are compounds that can clear senescent cells or modulate the release of SASP factors and hence attenuate the impact of the senescence-associated pro-inflammatory state. Phytochemicals, phenolic compounds and terpenes, which have antioxidant and anti-inflammatory activities, could also be senotherapeutic given their ability to act upon senescence-linked cellular pathways. The aim of this review is to dissect links among the gut microbiome, cellular senescence, inflammaging, and disease, as well as to explore phytochemicals as potential senotherapeutics, focusing on their interactions with gut microbiota. Coordinated targeting of these inter-related processes might unveil new strategies for promoting healthy aging.

Alzheimer's disease (AD) is the most common type of dementia which affects over than 60 million cases worldwide with higher incidence in low and middle-income countries by 2030. Based on the multifactorial nature of AD different risk factors are linked to the condition considering the brain's β-amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) as its primary hallmarks. Lately, viral photogenes specially after recent SARS-CoV-2 pandemic has gained a lot of attention in promoting the neurodegenerative disorder such as AD based on their capacity to increase the permeability of the blood-brain barrier, dysregulation of immune responses, and the impact on Aβ processing and phosphorylation of tau proteins. Therefore, in this review, we summarized the important association of viral pathogens and their mechanism by which they contribute with AD formation and development. AN OVERVIEW OF THE ROLES OF VIRAL PATHOGENS IN AD: According to this figure, viruses can infect neurons directly by modulating the BBB, transferring from endothelial cells to glial cells and then to neurons, increasing the Aβ deposition, and affecting the tau protein phosphorylation or indirectly through the virus's entrance and pathogenicity that can be accelerated by genetic and epigenetic factors, as well as chronic neuroinflammation caused by activated microglia and astrocytes.

MicroRNAs (miRNAs), referring to a type of non-coding RNAs functioning in various biological processes, participate in the pathophysiology of Alzheimer's disease (AD) through increasing amyloid-beta (Aβ) production, enhancing Tau phosphorylation, and inducing neuroinflammation. Meanwhile, extracellular vesicles (EVs) have been suggested as promising carriers of AD biomarkers as they possess the ability to transmit information from cerebral tissue to peripheral blood. Inspired by the above findings, we in this review systematically generalized the roles of miRNAs in AD and explored the potential of EV-packed miRNA as biomarkers for early diagnosis of AD. Through the detailed investigation, this review may highlight the promise of EV-packed miRNAs in advancing our understanding of AD, and underscore the imperative needs of further studies on their diagnostic potential.

Background: In recent years, changes in the incidence and mortality rates of nasopharyngeal carcinoma have occurred globally, across various regions, and among different countries. As a high incidence group, it is necessary to study the prevalence trend of middle-aged and elderly people.

Methods: Detailed information on NPC in middle-aged and elderly patients from 1990 to 2021 was collected from the Global Burden of Disease Database 2021 (GBD2021). Adopted incidence, mortality, disability-adjusted life-years (DALYs), sociodemographic index (SDI) and corresponding Estimated Annual Percentage Changes (EAPCs) to assess the burden of NPC in middle-aged and elderly patients. Additionally, a global risk attribution analysis was conducted, and a Bayesian age-period-cohort (BAPC) model was applied to project the global burden of NPC in middle-aged and elderly patients from 2021 to 2035.

Findings: Globally, the incidence cases of NPC in middle-aged and elderly people increased by 58.2 %, the numbers of death increased by 33.8 %, and the DALY increased by 42.1 %. However, the EAPCs values and upper limits in incidence, mortality and DALY rates were all less than 0, indicating a decreasing trend of incidence, mortality and disease burden. Both incidence and mortality rates were decreasing in high-incidence territories. Most regions were negatively correlated with the sociodemographic index. Males had obviously higher incidence and mortality of NPC in middle-aged and elderly patients than females. The highest incidences of nasopharyngeal carcinoma in middle-aged and elderly males were in the 65-69 age group, and the incidences in females did not change much among different age groups. We found that Alcohol use, Occupational risk and Tobacco were the major risk factors for NPC-related mortality in middle-aged and elderly patients.

Conclusion: Controllable etiology should be effectively controlled in the future.

Data availability: The data sets generated and/or analyzed during the current study are available in the GBD repository (https://vizhub.healthdata.org/gbd-results/). Data will be made available on request.

Musculoskeletal disorders (MSDs) comprise diverse conditions affecting bones, joints, and muscles, leading to pain and loss of function, and are one of the most prevalent and major global health concerns. One of the hallmarks of MSDs is DNA damage. Once accumulated in the cytoplasm, the damaged DNA is sensed by the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway, which triggers the induction of type I interferons and inflammatory cytokines. Thus, this pathway connects the musculoskeletal and immune systems. Inhibitors of cGAS or STING have shown promising therapeutic effects in the pre-clinical models of several MSDs. Systemic, chronic, low-grade inflammation (SCLGI) underlies the development and maintenance of many MSDs. Failure to resolve SCLGI has been hypothesized to play a critical role in the development of chronic diseases, suggesting that the successful resolution of SCLGI will result in the alleviation of their related symptomatology. The process of inflammation resolution is feasible by specialized pro-resolving mediators (SPMs), which are enzymatically generated from dietary essential polyunsaturated fatty acids (PUFAs). The supplementation of SPMs or their stable, small-molecule mimetics and receptor agonists has revealed beneficial effects in inflammation-related animal models, including arthropathies, osteoporosis, and muscle dystrophy, suggesting a translational potential in MSDs. In this review, we substantiate the hypothesis that the use of cGAS-STING signaling pathway inhibitors together with SCLG-resolving compounds may serve as a promising new therapeutic approach for MSDs.

Alzheimer's disease (AD) is the most common type of dementia and neurodegenerative disease characterized by neurofibrillary tangles (NFTs) and amyloid plaque. Familial AD is caused by mutations in the APP, PSEN1, and PSEN2 genes and these mutations result in the early onset of the disease. Sporadic AD usually affects older adults over the age of 65 years and is, therefore classified as late-onset AD (LOAD). Several risk factors associated with LOAD including the APOE gene have been identified. Moreover, GWAS studies have identified a wide array of genes and polymorphisms that are associated with LOAD risk. Currently, the diagnosis of AD involves the evaluation of memory and personality changes, cognitive impairment, and medical and family history to rule out other diseases. Laboratory tests to assess the biomarkers in the body fluids as well as MRI, CT, and PET scans to analyze the presence of plaques and NFTs are also included in the diagnosis of AD. It is important to diagnose AD before the onset of clinical symptoms, i.e. during the preclinical stage, to delay the progression and for better management of the disease. Research has been conducted to identify biomarkers of AD in the CSF, serum, saliva, and urine during the preclinical stage. Current research has identified several biomarkers and potential biomarkers in the body fluids that enhance diagnostic accuracy. Aside from genetics, other factors such as diet, physical activity, and lifestyle factors may influence the risk of developing AD. Clinical trials are underway to find potential biomarkers, diagnostic measures, and treatments for AD mainly in the preclinical stage. This review provides an overview of the genes and biomarkers of AD.

The complex pathophysiology of Alzheimer's disease (AD) poses challenges for the development of therapies. Recently, neuroinflammation has been identified as a key pathogenic mechanism underlying AD, while inflammation has emerged as a possible target for the management and prevention of AD. Several prior studies have demonstrated that medications modulating neuroinflammation might lessen AD symptoms, mostly by controlling neuroinflammatory signaling pathways such as the NF-κB, MAPK, NLRP3, etc, and their respective signaling cascade. Moreover, targeting these inflammatory modalities with inhibitors, natural products, and metabolites has been the subject of intensive research because of their anti-inflammatory characteristics, with many studies demonstrating noteworthy pharmacological capabilities and potential clinical applications. Therefore, targeting inflammation is considered a promising strategy for treating AD. This review comprehensively elucidates the neuroinflammatory mechanisms underlying AD progression and the beneficial effects of inhibitors, natural products, and metabolites in AD treatment.

Alzheimer's disease (AD) is the most common type of cognitive impairment. AD is closely related to orthopedic diseases, such as osteoporosis and osteoarthritis, in terms of epidemiology and pathogenesis. Brain and bone tissues can regulate each other in different manners through bone-brain axis. This article reviews the research progress of the relationship between AD and orthopedic diseases, bone-brain axis mechanisms of AD, and AD therapy by targeting bone-brain axis, in order to deepen the understanding of bone-brain communication, promote early diagnosis and explore new therapy for AD patients.

Alzheimer's disease (AD) is the most common neurodegenerative disorder that affects the cerebral cortex and hippocampus, and is characterised by progressive cognitive decline and memory loss. A recent report of a patient carrying a novel gain-of-function variant of RELN (H3447R, termed RELN-COLBOS) who developed resilience against presenilin-linked autosomal-dominant AD (ADAD) has generated enormous interest. The RELN-COLBOS variant enhances interactions with the apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDLR), which are associated with delayed AD onset and progression. These findings were validated in a transgenic mouse model. Reelin is involved in neurodevelopment, neurogenesis, and neuronal plasticity. The evidence accumulated thus far has demonstrated that the Reelin pathway links apolipoprotein E4 (ApoE4), amyloid-β (Aβ), and tubulin-associated unit (Tau), which are key proteins that have been implicated in AD pathogenesis. Reelin and key components of the Reelin pathway have been highlighted as potential therapeutic targets and biomarkers for AD.