The Organ-Joint Axes in Osteoarthritis: Significant Pathogenesis and Therapeutic Targets.

Osteoarthritis (OA), a prevalent age-related disease, is increasingly recognized as a multifactorial condition. This comprehensive review provides a multifaceted perspective on the organ-joint crosstalk contributing to OA, transcending the traditional focus on local joint pathology. Based on current research, we discussed the brain-joint, gut-joint, muscle-joint interactions in the etiology and progression of OA.

Histone Methylation, Energy Metabolism, and Alzheimer's Disease.

Alzheimer's disease (AD) is an insidious, progressive, and irreversible neurodegenerative disease characterized by the deposition of extracellular amyloid β-protein (Aβ) to form senile plaques and abnormal phosphorylation of intracellular tau protein to form neuronal fiber tangles. The pathogenesis of AD is complex, and there are several hypotheses, primarily including the Aβ cascade hypothesis, the neurofibrillary tangle hypothesis, the inflammatory hypothesis, and the cholinergic hypothesis. It has been suggested that the dysregulation of multiple energy metabolic pathways, especially mitochondria metabolism, may be related to the severity of AD pathology and disease symptoms in the brain.

Lifelong Glutathione Deficiency in Mice Increased Lifespan and Delayed Age-Related Motor Declines.

Glutathione (GSH) is a crucial redox scavenger, essential for maintaining cellular redox balance. This study explores the long-term effects of chronic GSH deficiency on lifespan, motor function, cognitive performance, redox status and inflammation. GCLM mice, with a 70-90% reduction in GSH levels, were compared to GCLM controls across their lifespan (5, 10 and 20 months).

Role of AMPK and Sirtuins in Aging Heart: Basic and Translational Aspects.

Aging is a key risk factor for numerous diseases, including cardiac diseases. High energy demands of the heart require precise cellular energy sensing to prevent metabolic stress. AMPK and sirtuins are key intracellular metabolic sensors regulating numerous cell functions, like mitochondrial function and biogenesis, autophagy, and redox balance.

Gut Microbiota-Immune System Interactions in Health and Neurodegenerative Diseases: Insights into Molecular Mechanisms and Therapeutic Applications.

The human body contains approximately 100 trillion microorganisms, predominantly within the gastrointestinal tract, collectively called the gut microbiota. Investigations have revealed the bidirectional communication between the gut microbiota and the brain, characterized as the "microbiota-gut-brain axis." This axis represents an important regulator of brain development and function, immune system development, and nutrient metabolism, making it a target for efforts to alleviate the development and progression of neurodegenerative diseases (NDDs).

Brain Resident Ly6C Monocytes Are Necessary for Maintaining Adult Hippocampal Neurogenesis.

Adult hippocampal neurogenesis (AHN) is crucial to various brain functions. Neurodegeneration, neuroinflammation and stress can impair AHN, contributing to the development of neurological and psychiatric disorders. Stress is known to extensively affect both the brain and peripheral immune system.

Harnessing BDNF Signaling to Promote Resilience in Aging.

As a key member of the neurotrophin family in the central nervous system, brain-derived neurotrophic factor (BDNF) plays a critical role in the maintenance and plasticity of the nervous system. Its innate neuroprotective advantage can also be shared with the brain when normal aging-dependent processes challenge neural circuits. The intricate relationship between BDNF and resilience during the aging process signifies the molecular mechanisms that underlie the maintenance and protection of brain function, such as cognition, movement and psychological well-being.

Aging Deteriorates Blood Brain Barrier Function and Polarizes Adaptive T Cell Expansion Contributing to Neurocognitive Damage in Experimental Cirrhosis.

Cirrhosis incidence is significantly increased with age and frequently complicated with neurocognitive dysfunction. We have evaluated the contribution of aging to neuroinflammation in the liver-brain axis in advanced chronic liver disease. Young (6-week-old) and old (9-month-old) mice were included in a 12-week protocol of CCl-induced cirrhosis.

APOE ε4 and Insulin Resistance Influence Path-Integration-Based Navigation through Distinct Large-Scale Network Mechanisms.

Path integration (PI), which supports navigation without external spatial cues, is facilitated by grid cells in the entorhinal cortex. These cells are often impaired in individuals at risk for Alzheimer's disease (AD). However, other brain systems can compensate for this impairment, especially when spatial cues are available.

The Impact of Aging on Neurological Diseases in the Elderly: Molecular Mechanisms and Therapeutic Perspectives.

With the progression of global aging, neurological diseases in elderly individuals have aroused widespread interest among researchers. Imbalances in the homeostasis of neuronal microenvironments, including neural progenitor cells and microglia, are the leading cause of worsening neurodegenerative diseases. The aging of various glial cells can further lead to abnormal functions in the central nervous system (CNS).

Mechanisms of the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans and Mammals and Its Roles in Striated Muscles.

Throughout the course of evolution, organisms and cells have evolved a suite of mechanisms to manage persistent stimuli, thereby preserving cellular and organismal homeostasis. Upon detecting stress signals, cells activate a transcriptional response termed the mitochondrial unfolded protein response (UPR). This response is crucial for maintaining protein homeostasis, facilitating mitochondrial function recovery, promoting cell survival, and ultimately influencing lifespan.

Plasma Neurodegenerative Biomarkers in Cognitively Preserved Nonagenarians.

Plasma biomarkers represent promising tools for the screening and diagnosis of patients with neurodegenerative conditions. However, it is crucial to account for the effects of aging on biomarker profiles, especially in the oldest segments of the population. Additionally, biomarkers in this sample can offer in vivo insights into the physiological mechanisms underlying brain aging while concomitantly supporting cognitive preservation.

Circulating Ketone Bodies, Pyruvate, and Citrate and Risk of Cognitive Decline, Structural Brain Abnormalities, and Dementia.

The relationship between key energy metabolites and brain health is not well understood. We investigated the association between circulating ketone bodies, pyruvate, and citrate with cognitive decline, structural brain characteristics, and risk of dementia. We measured ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone), pyruvate, and citrate species using NMR in plasma samples from 1,850 older adults in the Cardiovascular Health Study collected in 1989-90 or 1992-93.

Normal Bone Matrix Mineralization but Altered Growth Plate Morphology in the Lmna Mouse Model of Progeria.

Hutchison-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by a mutation in LMNA, the gene encoding A-type lamins, leading to premature aging with severely reduced life span. HGPS is characterized by growth deficiency, subcutaneous fat and muscle issue, wrinkled skin, alopecia, and atherosclerosis. Patients also develop a bone phenotype with reduced bone mineral density, osteolysis and striking demineralization of long bones.

Exercise Types: Physical Activity Mitigates Cardiac Aging and Enhances Mitochondrial Function via PKG-STAT3-Opa1 Axis.

Although age-related deterioration of the cardiac function is a well-studied area of research, the interventions and their molecular pathways have not yet been fully identified. Since physical activity is a powerful preventive measure against cardiac aging, our study compared the effects of long-term voluntary and forced physical activity with a sedentary group, utilizing an aging rat model characterized by mitochondrial dysfunction that contributes to age-related cardiovascular diseases. Four experimental groups were created: (I) young controls (12-week-old); (II) 18-month-old aged sedentary rats; (III) aged group with free access to running wheels for 6 months; (IV) aged rats subjected to forced physical activity for 6 months.

The Expanding Burden of Neurodegenerative Diseases: An Unmet Medical and Social Need.

Neurodegenerative diseases, particularly Alzheimer's disease and other dementias as well as Parkinson's disease, are emerging as profoundly significant challenges and burdens to global health, a trend highlighted by the most recent Global Burden of Disease (GBD) 2021 studies. This growing impact is closely linked to the demographic shift toward an aging population and the potential long-term repercussions of the COVID-19 pandemic, both of which have intensified the prevalence and severity of these conditions. In this review, we explore several critical aspects of this complex issue, including the increasing global burden of neurodegenerative diseases, unmet medical and social needs within current care systems, the unique and amplified challenges posed by the COVID-19 pandemic, and potential strategies for enhancing healthcare policy and practice.

Differential Roles of Astrocytic CSF1 in Alzheimer's Disease and Cerebral Amyloid Angiopathy: Insights from Transcriptomic Analysis.

Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) are neurodegenerative disorders characterized by the pathological deposition of amyloid-beta (Aβ) in the brain. Although both conditions share common pathogenic pathways, they exhibit distinct cellular manifestations and disease progression. This study focused on the differential expression and role of astrocytic colony-stimulating factor 1 (CSF1) in these diseases.

Bidirectional Crosstalk between the Heart and Brain in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder condition linked to various systemic comorbidities. Numerous studies have shown bidirectional crosstalk between the heart and the brain, but the specifics of how these interactions occur in AD are poorly understood. This narrative review summarizes the clinical evidence for a firm link between AD and cardiovascular health and discusses the bidirectional roles of AD and the cardiovascular system.

The Impact of Aging on Ocular Diseases: Unveiling Complex Interactions.

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. Aging is an important risk factor for eye diseases. The gradual deterioration of ocular tissue structure and function with age leads to the onset and progression of ocular diseases.

Time and Tissue Windows in Futile Reperfusion after Ischemic Stroke.

Reperfusion strategies such as vascular thrombolysis and thrombectomy are the first-line treatments recommended for acute ischemic stroke. However, only half of these patients achieve functional independence after endovascular reperfusion of large vessel occlusions. Timely restoration of blood flow is crucial, but not all reperfusion results in benefit, a phenomenon termed futile reperfusion.