Aggregator

Scientists have uncovered why two seemingly opposite ways of targeting the same brain receptor can both promote weight loss. In mice, activating the GIP receptor in the brainstem reduced appetite, while blocking it in the hypothalamus removed a kind of “brake” on fullness signals. The discovery helps explain why very different obesity drugs can achieve similar results and suggests that carefully combining GIP-targeting treatments with GLP-1 drugs like those related to Wegovy and Ozempic could produce stronger effects.

Scientists have discovered that the aging human brain may be far less isolated from the rest of the body than once believed. Stanford researchers found that large numbers of immune cells from the blood begin entering the brain as early as middle age, where they can transform into microglia, the brain’s specialized immune cells. The finding overturns a long-standing assumption that these cells remain largely separate from the body’s immune system throughout life.

Simply choosing the stairs could have surprisingly big benefits for your heart and longevity. A large analysis involving more than 480,000 people found that regular stair climbers were 39% less likely to die from cardiovascular disease and 24% less likely to die from any cause than people who rarely took the stairs. They also had lower risks of heart attack, stroke, and heart failure.

A surprising stress-related signal may help the brain repair itself after injury. Researchers found that myelin-producing precursor cells rapidly release the stress hormone CRH near damaged brain tissue, helping control how those cells mature and rebuild protective nerve insulation. The same system also influences brain development and the thickness of myelin later in life. The findings could offer new clues about how early-life stress contributes to psychiatric disorders.

Women who used estrogen-only hormone therapy later in life were less likely to develop dementia and showed fewer signs of Alzheimer’s disease in their brains, according to a large study of more than 21,000 participants. Hormone therapy use was linked to 39% lower odds of a dementia diagnosis and 35% lower odds of Alzheimer’s-related brain changes at autopsy, including amyloid plaques and tau tangles. Biomarker tests also suggested less amyloid buildup among hormone therapy users.

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular...

CONCLUSIONS: Exercise improves balance, but modality choice should consider balance domain. Current estimates were most favourable for perturbation training in overall and static balance under supervision, sensory training at home, Tai Chi in global balance, Pilates in dynamic balance, and agility stepping or aquatic exercise in proactive balance. These estimates do not establish superiority. Dose should reflect task-specific challenge, safety and feasibility, because METs capture metabolic cost...

CONCLUSION: Moderate levels of green and blue spaces were associated with lower levels of biological aging. Nonlinear associations were stronger in socially vulnerable groups, suggesting that equitable nature-based planning could be a strategic public health intervention to promote healthy aging.

Graph theory provides unique tools to assess complex networks. It has been previously used with functional magnetic resonance imaging (fMRI) datasets to quantify macroscopic-scale connections among different brain regions, readily capturing brain network changes in subjects with Alzheimer's disease. Here, we apply graph theory to miniscope calcium imaging data recorded from the prefrontal cortex of freely behaving wild-type (WT) and Shank3^(fx) mice (a mouse model of autism) during social...

The choroid plexus (ChP) regulates cerebrospinal fluid homeostasis and immune surveillance, but its cellular organization and response to Alzheimer's disease (AD) remain incompletely defined. Here, we integrate single-nucleus RNA sequencing with spatial transcriptomics to generate a high-resolution atlas of the adult human ChP. We identify all major epithelial, stromal, and immune populations and resolve heterogeneity within macrophages, including a distinct subset expressing the giant protein...

Social interaction regulates neuronal excitability and behavior, and the lateral septum (LS) plays an important role in social behavior. However, the molecular mechanisms that support LS-dependent social responses remain unclear. Here, we show that neuronal activity-driven glucose transporter 4 (GLUT4) plasma translocation in LS GABAergic neurons supports social familiarity. Neuronal activation triggers CaMKIIα-mediated phosphorylation of GLUT4 at Ser243 and Ser254, which enhances Rab10 binding,...

The integrated stress response (ISR) enables cells to adapt to diverse cellular stresses, but during chronic or unresolved stress it becomes maladaptive and is implicated in neurodegenerative diseases, including Parkinson disease (PD). The mechanisms underlying maladaptive ISR-driven neurodegeneration, however, remain poorly defined. Here, we find a critical pathway by which chronic ISR activation promotes neurodegeneration in neurotoxin and α synucleinopathy models of PD in vitro and in vivo....

Gamma wave entrainment is a promising approach for improving cognitive function, particularly in the early stages of Alzheimer's disease. However, for everyday treatment, a light source system that maintains visibility while delivering effective stimulation is essential for patient comfort and practicality. To address this need, we developed organic light-emitting diode (OLED) glasses with optimized large-area transparent OLEDs for gamma wave entrainment. The optimization involved all layers of...

The choroid plexus (ChP) regulates cerebrospinal fluid homeostasis and immune surveillance, but its cellular organization and response to Alzheimer's disease (AD) remain incompletely defined. Here, we integrate single-nucleus RNA sequencing with spatial transcriptomics to generate a high-resolution atlas of the adult human ChP. We identify all major epithelial, stromal, and immune populations and resolve heterogeneity within macrophages, including a distinct subset expressing the giant protein...

Perovskite solar cells (PSCs) using self-assembled monolayers (SAMs) as hole transporting materials have achieved impressive efficiencies. However, the vulnerability of SAMs causes desorption under light and thermal stress. While various modifications to the conjugated core and anchoring group of SAMs have been explored, challenges in balancing efficiency and stability remain. Here, we introduce a new class of cross-linkable SAMs, uniquely functionalized at the molecular linker. Upon in situ...

In Alzheimer's disease, the protein tau is thought to redistribute from axons to the somatodendritic compartment and form fibrillar aggregates. Although tau aggregation is a hallmark of Alzheimer's disease, the dynamics of its synthesis and degradation are not well characterized. Given that nascent polypeptides are particularly susceptible to misfolding, local control of tau synthesis and degradation may be essential to prevent aggregation. Here we develop STARFISH, a method for visualizing the...

Aging-related metabolic decline, particularly impaired glucose tolerance, represents a growing challenge in aging populations. Probiotics are promising modulators of host metabolism; however, how sex differences influence their efficacy in mitigating metabolic aging remains poorly understood. Here, we administered Lactiplantibacillus plantarum AS21 to naturally aged male and female mice for 6 months. We observed a pronounced sexual dimorphism in metabolic decline, with aged males exhibiting more...

CONCLUSIONS: Storey configuration and number of transition points constitute structural conditions that shape outdoor access in RCFs. These findings have implications for age-friendly design and planning of RCFs as well as for person-centred care and rehabilitation.

Endolysosomal membranes are frequently damaged by pathogenic stress associated with aging, infection, and neurodegeneration, and failure to repair such damage leads to inflammation and cell death. Recent advances identify membrane ATG8 conjugation (atg8ylation) as a key process that links damage detection to coordinated lysosomal repair, removal, and regeneration. Beyond its canonical role in macroautophagy, membrane atg8ylation also occurs on preexisting, non-autophagosomal single membranes...

CONCLUSION: Commonly used claims-based algorithms to identify ADRD had reasonable validity, though each presented important context-dependent tradeoffs and none was uniformly superior. These findings highlight the importance of accurately diagnosing ADRD in clinical settings and of understanding each algorithm's strengths and limitations based on the use case. Limitations include that NHATS is not a "gold standard" for comparison of claims-based algorithms and we only analyzed NHATS respondents...