Aging and Disease最新文献

Increased entropy is a common cause of disease and aging. Lifespan entropy is the overall increase in disorder caused by a person over their lifetime. Aging leads to the excessive production of reactive oxygen species (ROS), which damage the antioxidant system and disrupt redox balance. Organ aging causes chronic inflammation, disrupting the balance of proinflammatory and anti-inflammatory factors. Inflammaging, which is a chronic low-grade inflammatory state, is activated by oxidative stress and can lead to immune system senescence. During this process, entropy increases significantly as the body transitions from a state of low order to high disorder. However, the connection among inflammation, aging, and immune system activity is still not fully understood. This review introduces the idea of the ROS-inflammation-immune balance for the first time and suggests that this balance may be connected to aging and the development of age-related diseases. We also explored how the balance of these three factors controls and affects age-related diseases. Moreover, imbalance in the relationship described above disrupts the regular structures of cells and alters their functions, leading to cellular damage and the emergence of a disorganized state marked by increased entropy. Maintaining a low entropy state is crucial for preventing and reversing aging processes. Consequently, we examined the current preclinical evidence for antiaging medications that target this balance. Ultimately, comprehending the intricate relationships between these three factors and the risk of age-related diseases in organisms will aid in the development of clinical interventions that promote long-term health.

The gut-brain axis is a bidirectional communication pathway that modulates cognitive function. A dysfunctional gut-brain axis has been associated with cognitive impairments during aging. Therefore, we propose evaluating whether modulation of the gut microbiota through fecal microbiota transplantation (FMT) from young-trained donors (YT) to middle-aged or aged mice could enhance brain function and cognition in old age. Twelve-month-old male mice received an initial FMT from YT (YT-Tr) or age-matched donors (Auto-Tr) following antibiotic treatment. Three months later, the mice received a second FMT as reinforcement. Additionally, 18-month-old mice received Auto-Tr, YT-Tr, or FMT from young sedentary donors (YS-Tr). Cognitive function was assessed using novel object recognition and object location memory tests. Long-term potentiation (LTP) in hippocampal brain slices was studied, while neuroinflammation and synaptic plasticity were analyzed in hippocampal samples via qPCR and immunoblot. Gut permeability was evaluated in ileum and colon sections, serum samples were analyzed for cytokine levels, and fecal samples were used to measure short-chain fatty acid (SCFA) levels and perform 16S rRNA gene sequencing. We observed that YT-Tr, whether performed in middle age or old age, improved cognitive function in aged mice. Recognition and spatial memory were significantly enhanced in YT-Tr mice compared to Auto-Tr and YS-Tr groups. Intact LTP was observed in YT-Tr mice at 18 months of age, whereas LTP was impaired in the Auto-Tr group. Neuroinflammation was reduced, and synaptic plasticity modulators such as PSD-95 and FNDC5/Irisin were upregulated in the hippocampus of YT-Tr mice compared to both YS-Tr and Auto-Tr groups. A significant reduction in ileal and colon permeability was detected in YT-Tr animals, along with elevated cecal levels of butyrate and valerate compared to Auto-Tr. Moreover, YT-Tr decreased pro-inflammatory factors and increased anti-inflammatory factors in the serum of aged mice. Beta diversity analysis revealed significant differences in microbial community composition between YT-Tr and Auto-Tr animals, with higher abundances of Akkermansia, Prevotellaceae_UCG-001, and Odoribacter in YT-Tr mice. In conclusion, our study demonstrates that FMT from young-trained donors improves cognitive function and synaptic plasticity by modulating gut permeability, inflammation, SCFA levels, and gut microbiota composition in aged mice.

Aging is a complex and universal process marked by gradual functional declines at the cellular and tissue levels, often leading to a range of aging-related diseases such as diabetes, cardiovascular diseases, and cancer. Delaying the aging process can help prevent, slow down, and alleviate the severity of these various conditions, enhancing overall health and well-being. Alpha-glucosidase inhibitors (AGIs) are a class of widely used antidiabetic drugs that inhibit alpha-glucosidase in the small intestinal mucosa, delaying carbohydrate absorption and reducing postprandial hyperglycemia. Beyond their roles in diabetes treatment, AGIs have shown potential in extending lifespan and effectively treating aging-related diseases by modulating oxidative stress, gut microbiota, inflammatory responses, and nutrient-sensing pathways. This review summarizes recent advancements in the application of AGIs for preventing and treating aging and aging-related diseases, with a focus on their mechanisms and roles in these processes.

Circadian rhythm is the internal homeostatic physiological clock that regulates the 24-hour sleep/wake cycle. This biological clock helps to adapt to environmental changes such as light, dark, temperature, and behaviors. Aging, on the other hand, is a process of physiological changes that results in a progressive decline in cells, tissues, and other vital systems of the body. Both aging and the circadian clock are highly interlinked phenomena with a bidirectional relationship. The process of aging leads to circadian disruptions while dysfunctional circadian rhythms promote age-related complications. Both processes involve diverse physiological, molecular, and cellular changes such as modifications in the DNA repair mechanisms, mechanisms, ROS generation, apoptosis, and cell proliferation. This review aims to examine the role of aging and circadian rhythms in the context of lung cancer. This will also review the existing literature on the role of circadian disruptions in the process of aging and vice versa. Various molecular pathways and genes such as BMAL1, SIRT1, HLF, and PER1 and their implications in aging, circadian rhythms, and lung cancer will also be discussed.

With complex pathogenesis, Alzheimer's disease (AD) is a neurological illness that has worsened over time. Inter-organ crosstalk, which is essential for coordinating organ function and maintaining homeostasis, is involved in multiple physiological and pathological events. Increasing evidence suggests that AD is closely associated with multiple diseases of peripheral organs, including the gut, adipose tissue, liver, and bone. Despite numerous studies on AD, the ambiguous role of pathological peripheral organ-brain crosstalk in the development of AD remains incompletely understood, and the potential mechanisms remain obscure. This review summarizes the current knowledge of the relationship between AD and disorders of various organs from clinical and preclinical evidence. Additionally, we elucidate the mechanisms underlying AD development from the perspective of "organ-organ crosstalk", including the gut-brain, adipose tissue-brain, liver-brain and bone-brain axes. On the basis of the peripheral organ-brain crosstalk, we emphasize promising therapeutic targets with the hope of providing novel perspectives for AD management.

Lung cancer treatment is evolving, and the role of senescent macrophages in tumor immune evasion has become a key focus. This study explores how senescent macrophages interact with lung cancer cells, contributing to tumor progression and immune dysfunction. As aging impairs macrophage functions, including phagocytosis and metabolic signaling, it promotes chronic inflammation and cancer development. p16^INK4a-positive macrophages are common in aged mice, and their clearance slows tumor growth, suggesting these cells support tumor proliferation and immune evasion. Targeting the senescence-associated secretory phenotype (SASP) and reprogramming senescent macrophages offers potential therapeutic benefits, including reversing immune aging and boosting anti-tumor immunity. However, translating these findings into clinical practice requires further molecular understanding and rigorous clinical trials.

The complex set of interactions between the immune system and metabolism, known as immunometabolism, has emerged as a critical regulator of disease outcomes in the central nervous system. Numerous studies have linked metabolic disturbances to impaired immune responses in brain aging, neurodegenerative disorders, and brain injury. In this review, we will discuss how disruptions in brain immunometabolism balance contribute to the pathophysiology of brain dysfunction. The first part of the review summarizes the contributions of critical immune cell populations such as microglia, astrocytes, and infiltrating immune cells in mediating inflammation and metabolism in CNS disorders. The remainder of the review addresses the impact of metabolic changes on immune cell activation and disease progression in brain aging, Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, spinal cord injury, and traumatic brain injury. Furthermore, we also address the therapeutic potential of targeting immunometabolic pathways to reduce neuroinflammation and slow disease progression. By focusing on the interactions among brain immune cells and the metabolic mechanisms they recruit in disease, we present a comprehensive overview of brain immunometabolism in human health and disease.

Osteoarthritis (OA) is a multifaceted degenerative joint disorder affected by various risk factors such as age, mechanical stress, inflammation, and metabolic influences. These elements contribute to its diverse phenotypes and endotypes, underscoring the disease's inherent complexity. The involvement of multiple tissues and their interplay further complicates OA's investigation. The current limitations in spatial phenotyping technologies, coupled with the intricate web of multifactorial interactions, have hindered the discovery of reliable early diagnostic markers and the development of tailored therapeutic strategies. However, recent advances in spatiotemporal analysis have revolutionised researchers' capacity to explore OA's spatiotemporal dynamics. These advancements provide unprecedented insights into the disease's progression, revealing patient-specific clinical presentations, tissue and joint structure alterations, and microscopic to molecular changes in tissue cell populations and extracellular matrices. This paper summarises the latest developments in utilising state-of-the-art technologies for the deep phenotyping of OA's spatiotemporal variations, emphasising their critical role in elucidating OA's pathophysiology and how this can change clinical practice and advancing personalised treatment approaches, and finally lead to better clinical outcomes.

This review summarizes the mechanism and role of physical activity in maintaining the proper functioning of the musculoskeletal system. Bone adaptation to the mechanical environment occurs in skeletal regions subjected to the greatest stresses resulting from the nature of exercise, however, there is a varied response of bone tissue to mechanical loads depending on its material and structural properties (trabecular and cortical). The regulation of bone tissue metabolism during physical exercise is influenced by factors associated with mechanical stress (gravitational forces, impact loading, and muscular contractions) as well as by systemic mechanisms (hormones, myokines, cytokines). The presence of insulin receptors and glucose transporters in osteoblasts indicates that these cells consume large amounts of glucose. Therefore, when energy demand during physical activity increases, nutritional factors play an important role in bone response. On the other hand, the musculoskeletal system participates in the regulation of energy metabolism. To maintain bone homeostasis, an optimized form of physical activity should be used (e.g. intensity, duration, training session frequency). The complexity of factors modulating the sensitivity of bones to mechanical stimuli causes the results of physical training are age- and sex-dependent. Moreover, when selecting exercises to improve bone health, it is important to take into account metabolic and musculoskeletal system conditions. In addition, exercise should be safe and adapted to the health and fitness level so as not to increase the risk of fractures. Participation in regular physical activity should continue after the training program to maintain bone mass.

Ferroptosis, an iron-dependent form of programmed cell death driven by oxidative stress, plays a crucial role in the progression of Alzheimer's disease (AD). Aging diminishes antioxidant systems that maintain iron homeostasis, particularly affecting the glutathione peroxidase (GPX) system, leading to increased ferroptosis and exacerbated neurodegeneration and neuroinflammation in AD. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating genes involved in antioxidant defense and ferroptosis. In this review, we examine the interconnected roles of Nrf2 signaling, iron metabolism, and ferroptosis in AD, and discuss how regular physical exercise-known to enhance antioxidant capacity-might influence these processes. Despite evidence linking exercise to improved cognitive function in AD and its role in modulating oxidative stress, there is a paucity of research specifically addressing how exercise affects ferroptosis in the AD brain. To address this gap, we utilized bioinformatics techniques to identify potential pathways and mechanisms by which exercise may mitigate ferroptosis in AD through Nrf2 signaling. Analyzing gene expression profiles from the GEO database, we identified differentially expressed ferroptosis-related genes in the hippocampus following exercise intervention. Hub genes like SLC2A1, TXN, MEF2C, and KRAS were significantly upregulated, suggesting that exercise may activate a network enhancing antioxidant defenses and regulating iron metabolism via Nrf2. Our findings propose a novel mechanism whereby exercise alleviates abnormal ferroptosis in the AD brain through modulation of Nrf2 signaling. This study highlights the need for further research to validate these findings and explore exercise as a therapeutic strategy for AD by targeting ferroptosis.