Core Viewpoint - The article emphasizes the detrimental effects of prolonged sedentary behavior on both physical and cognitive health, highlighting the urgent need for integrating movement into daily routines to combat metabolic disorders and cognitive decline [8][11][15]. Group 1: Sedentary Lifestyle and Health Risks - A study reveals that just 10 days of inactivity can significantly worsen insulin resistance and increase the risk of cognitive decline through muscle-brain axis disruptions [8][9]. - Data indicates that from 1940 to 2020, while global life expectancy increased by 12.6 years, the prevalence of type 2 diabetes surged by 4.7 times, and healthy life expectancy after age 65 decreased by 8.2 years [11][12]. - Urban professionals are reported to sit for over 9 hours a day, with 83% relying on screens during leisure time, contributing to metabolic crises [14]. Group 2: Mechanisms of Cognitive Decline - Muscle disuse leads to iron overload in skeletal muscles while decreasing iron levels in serum and brain tissue, creating a negative correlation that exacerbates insulin resistance and neuroinflammation [8][9]. - The study identifies a new mechanism where muscle atrophy affects cognitive decline through iron metabolism regulation, suggesting that even short-term inactivity could be a potential trigger for Alzheimer's disease [9]. Group 3: Benefits of Physical Activity - Engaging in regular physical activity can yield immediate and long-term health benefits, including a 33% reduction in all-cause mortality risk for those who incorporate movement into their routines [16][17]. - The concept of "exercise investment" is introduced, indicating that the metabolic memory effect from exercise can sustain pancreatic and brain health, making any time to start exercising worthwhile [16][17]. - Regular exercise can enhance insulin sensitivity by 25% and reduce dementia risk by 28% compared to sedentary individuals [16][17]. Group 4: Strategies for Incorporating Movement - The article suggests four simple strategies to develop exercise habits, such as creating more opportunities for activity in daily life, incorporating short breaks for movement during work, engaging in outdoor activities on weekends, and setting achievable goals [18][19]. - Small changes, like walking an additional 2,000 steps daily, can significantly lower cardiovascular disease risk by 15% [18]. - Establishing a consistent exercise routine is emphasized as more important than the intensity of workouts, with gradual increases in activity recommended [19].

Core Findings - A team from the University of California, Irvine discovered that a combination of Vitamin B3 (niacinamide) and the active component in green tea, EGCG, can rejuvenate aging brain cells and effectively clear harmful protein accumulations associated with Alzheimer's disease [1][2] - The research published in the latest issue of "Aging Science" indicates that this combination significantly enhances the levels of GTP, a key energy molecule in brain cells, and improves the ability to clear β-amyloid proteins, which are characteristic of Alzheimer's disease [1][3] Mechanism of Action - The study utilized a gene-encoded fluorescent sensor named GEVAL to monitor GTP dynamics in neurons of aged Alzheimer's model mice, revealing a continuous decline in GTP levels with age, particularly in mitochondria, which severely impacts autophagy, the process of clearing damaged components [1] - Neurons treated with niacinamide and EGCG showed GTP levels restored to those of younger cells, leading to improved energy metabolism, activation of key proteins responsible for cellular transport, and efficient clearance of β-amyloid aggregates, thereby reducing oxidative stress associated with neurodegeneration [2] Implications for Treatment - The findings suggest that the combination of these two natural dietary supplements may serve as a new tool in combating cognitive decline and Alzheimer's disease [3]

Core Viewpoint - The research reveals the developmental control mechanism of the meningeal lymphatic system in the brain, highlighting the dynamic regulation by neural activity through specific glial cell subtypes, which provides new insights into the interaction between the nervous and immune systems [3][6][9]. Group 1: Research Findings - The study identifies that neural activity regulates the expression of Vegfc in slc6a11b+ radial astrocytes, which in turn controls the development of mural lymphatic endothelial cells (muLEC) in the meninges [3][5]. - It demonstrates that slc6a11b+ radial astrocytes are the primary source of Vegfc, essential for muLEC development, and that this process is modulated by neural activity [7][9]. - The collaboration between slc6a11b+ radial astrocytes and ccbe1+ fibroblasts ensures that muLEC is restricted to the brain surface, preventing invasion into the brain parenchyma [5][9]. Group 2: Implications for Future Research - The findings suggest that the brain not only processes neural information but also coordinates its microenvironment, providing a new framework for understanding brain-immune interactions [9]. - The research opens avenues for interventions targeting this regulatory network, potentially offering new perspectives on the role of the meningeal lymphatic system in neurodegenerative diseases [9][14]. - It emphasizes the importance of a functional lymphatic network for brain health, indicating that targeting the external lymphatic pathways may enhance treatment efficacy for neurological disorders [14].