Ageing research reviews最新文献

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.

Cardio-cerebral diseases (CCDs), encompassing conditions such as coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, et al., represent a significant threat to human health and well-being. These diseases are often characterized by metabolic abnormalities and remodeling in the process of pathology. Glycolysis and hypoxia-induced lactate accumulation play critical roles in cellular energy dynamics and metabolic imbalances in CCDs. Lactylation, a post-translational modification driven by excessive lactate accumulation, occurs in both histone and non-histone proteins. It has been implicated in regulating protein function across various pathological processes in CCDs, including inflammation, angiogenesis, lipid metabolism dysregulation, and fibrosis. Targeting key proteins involved in lactylation, as well as the enzymes regulating this modification, holds promise as a therapeutic strategy to modulate disease progression by addressing these pathological mechanisms. This review provides a holistic picture of the types of lactylation and the associated modifying enzymes, highlights the roles of lactylation in different pathological processes, and synthesizes the latest clinical evidence and preclinical studies in a comprehensive view. We aim to emphasize the potential of lactylation as an innovative therapeutic target for preventing and treating CCD-related conditions.

Neurodegenerative diseases (NDDs) are a group of neurological disorders characterized by the progressive loss of neuronal structure and function, leading to cognitive and behavioral impairments. Despite significant research advancements, there is currently no definitive cure for NDDs. With global aging on the rise, the burden of these diseases is becoming increasingly severe, highlighting the urgency of understanding their pathogenesis and developing effective therapeutic strategies. Microglia, specialized macrophages in the central nervous system, play a dual role in maintaining neural homeostasis. They are involved in clearing cellular debris and apoptotic cells, but in their activated state, they release inflammatory factors that contribute significantly to neuroinflammation. The complement system (CS), a critical component of the innate immune system, assists in clearing damaged cells and proteins. However, excessive or uncontrolled activation of the CS can lead to chronic neuroinflammation, exacerbating neuronal damage. This review aims to explore the roles of microglia and the CS in the progression of NDDs, with a specific focus on the mechanisms through which the CS activates microglia by modulating mitochondrial function. Understanding these interactions may provide insights into potential therapeutic targets for mitigating neuroinflammation and slowing neurodegeneration.

The rapid aging of the global population necessitates addressing age-related conditions through innovative strategies. Nutritional supplements have emerged as potential interventions for preventing or slowing age-related changes, with betaine being a promising candidate. This systematic review aims to provide a comprehensive analysis of current literature on the impact of betaine on the aging process. Specifically, we summarize the mechanisms through which betaine is proposed to affect aging, we integrate existing findings, we identify gaps in the literature, and we discuss practical implications for promoting healthy aging. Evidence suggests that betaine may counteract aging-related changes in methylation potential by increasing concentration of S-adenosylmethionine, a key methyl donor. Additionally, betaine reduces homocysteine concentrations, potentially mitigating vascular, neurodegenerative, and oxidative damage. Betaine has also been shown to enhance mitochondrial function, to reduce oxidative stress, and to attenuate inflammation. It may serve as a preventive agent against sarcopenia by promoting anabolic signaling pathways and improving muscle strength in younger adults. Betaine may also exert an effect on bone remodeling and adipose tissue metabolism, with animal studies indicating enhanced fat oxidation and reduced fat synthesis. Although certain limited studies have suggested betaine's potential in mitigating age-related neurodegenerative diseases, the currently available evidence does not establish a clear link between dietary betaine intake and the incidence of cardiovascular diseases or type-2 diabetes. In conclusion, emerging evidence highlights the potential of betaine in attenuating age-related changes. However, further research is required to elucidate the efficacy and safety of betaine supplementation in older populations.

Acute myocardial infarction (AMI), primarily caused by coronary atherosclerosis, initiates a series of events that culminate in the obstruction of coronary arteries, resulting in severe myocardial ischemia and hypoxia. The subsequent myocardial ischemia/reperfusion (I/R) injury further aggravates cardiac damage, leading to a decline in heart function and the risk of life-threatening complications. The complex interplay of multiple regulated cell death (RCD) pathways plays a pivotal role in the pathogenesis of AMI. Each RCD pathway is orchestrated by a symphony of molecular regulatory mechanisms, highlighting the dynamic changes and critical roles of key effector molecules. Strategic disruption or inhibition of these molecular targets offers a tantalizing prospect for mitigating or even averting the onset of RCD, thereby limiting the extensive loss of cardiomyocytes and the progression of detrimental myocardial fibrosis. This review systematically summarizes the mechanisms underlying various forms of RCD, provides an in-depth exploration of the pathogenesis of AMI through the lens of RCD, and highlights a range of promising therapeutic targets that hold the potential to revolutionize the management of AMI.

The field of aging and longevity research is overwhelmed by vast amounts of data, calling for the use of Artificial Intelligence (AI), including Large Language Models (LLMs), for the evaluation of geroprotective interventions. Such evaluations should be correct, useful, comprehensive, explainable, and they should consider causality, interdisciplinarity, adherence to standards, longitudinal data and known aging biology. In particular, comprehensive analyses should go beyond comparing data based on canonical biomedical databases, suggesting the use of AI to interpret changes in biomarkers and outcomes. Our requirements motivate the use of LLMs with Knowledge Graphs and dedicated workflows employing, e.g., Retrieval-Augmented Generation. While naive trust in the responses of AI tools can cause harm, adding our requirements to LLM queries can improve response quality, calling for benchmarking efforts and justifying the informed use of LLMs for advice on longevity interventions.

Since the first description of a set of characteristics of aging as so-called hallmarks or pillars in 2013/2014, these characteristics have served as guideposts for the research in aging biology. They have been examined in a range of contexts, across tissues, in response to disease conditions or environmental factors, and served as a benchmark for various anti-aging interventions. While the hallmarks of aging were intended to capture generalizable characteristics of aging, they are derived mostly from studies of rodents and humans. Comparative studies of aging including species from across the animal tree of life have great promise to reveal new insights into the mechanistic foundations of aging, as there is a great diversity in lifespan and age-associated physiological changes. However, it is unclear how well the defined hallmarks of aging apply across diverse species. Here, we review each of the twelve hallmarks of aging defined by Lopez-Otin in 2023 with respect to the availability of data from diverse species. We evaluate the current methods used to assess these hallmarks for their potential to be adapted for comparative studies. Not unexpectedly, we find that the data supporting the described hallmarks of aging are restricted mostly to humans and a few model systems and that no data are available for many animal clades. Similarly, not all hallmarks can be easily assessed in diverse species. However, for at least half of the hallmarks, there are methods available today that can be employed to fill this gap in knowledge, suggesting that these studies can be prioritized while methods are developed for comparative study of the remaining hallmarks.

Alzheimer's disease, a progressive neurodegenerative pathology, is characterized by the accumulation of Amyloid-β plaques in the brain. Lecanemab (BAN2401), a humanized IgG1 monoclonal antibody, binds with high affinity to Amyloid-β protofibrils. It is the first monoclonal antibody for Alzheimer's disease to receive full FDA approval. This systematic review, conducted meticulously, examines the current use and safety of Lecanemab in treating Alzheimer's disease. We screened literature from databases such as PubMed Central, PubMed (MedLine), ScienceDirect, Scopus, Web of Science, and Wolters Kluwer for randomized controlled trials testing Lecanemab for cognitive decline in patients with mild cognitive impairment due to Alzheimer's disease. Outcomes measured included CDR-SB, ADCOMS, ADAS-Cog, and Amyloid burden on PET in centiloids. Likewise, reports were analyzed for adverse events associated with ARIA-A and ARIA-H. Five papers were included in the systematic review and three in the meta-analysis. The meta-analysis showed that Lecanemab slowed the progression of cognitive impairment as measured by CDR-SB, ADCOMS, and ADASCog, and significantly reduced Amyloid burden on PET in centiloids. However, Lecanemab was associated with an increased risk of ARIA-E and ARIA-H. Lecanemab has demonstrated efficacy in slowing cognitive impairment progression in Alzheimer's disease as measured by ADCOMS, ADAS-Cog, and CDR-SB. However, it is associated with an increased risk of ARIA-E and ARIA-H, particularly in ApoE4 carriers.