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A specially engineered chewing gum reduced HPV by up to 93% and nearly eliminated two bacteria linked to head and neck cancer. The treatment preserved beneficial mouth bacteria, raising hopes for a safer and more affordable therapy.

Metabolic dysfunction is a defining but poorly understood feature of Alzheimer's disease. Du et al. show that a brain-penetrant GLP-1 receptor agonist rewires astrocyte-neuron metabolic coupling through lactate-driven histone lactylation, linking astrocytic glycolysis to neuronal lipid homeostasis and positioning metabolite signaling as a therapeutic axis in neurodegeneration.

Alzheimer's disease (AD), as the leading cause of dementia, poses an increasingly severe socioeconomic burden in the context of global ageing. Traditionally defined by amyloid-β and tau pathology, it's increasingly recognized as a systems disorder in which impaired glucose metabolism, mitochondrial dysfunction, and neuroinflammation interact across neural cell types and disease stages. However, the interaction among these three mechanisms, their role in promoting the classical pathology of AD,...

Metabotropic glutamate receptor subtype 5 (mGlu5) is an important regulator of excitatory neurotransmission and remains a therapeutic target for neuropsychiatric and neurological disorders, including substance use disorders, depression, Fragile X syndrome, Parkinson's disease-related dyskinesia, and other movement disorders. However, the clinical development of mGlu5 negative allosteric modulators (NAMs) has been limited by translational challenges, inconsistent efficacy, and safety concerns,...

Postural and locomotor dysfunction represent axial symptoms of Parkinson's disease (PD), which remain poorly treated by medication and deep brain stimulation. Whilst non-invasive neuromodulation of the vestibular system via the vestibular nucleus complex (VNC) offers a novel therapeutic avenue, the underlying circuits are still poorly characterized. Here we show that the mouse VNC feeds extensive Vglut2-defined projections into striato-thalamo-subthalamic and caudal medulla motor hubs and...

CONCLUSIONS AND IMPLICATIONS: Community-based implementation of the WHO ICOPE pathway within routine systems is feasible and identified substantial multidomain IC impairment among otherwise independent older adults. Variation across sites highlights the need for context-specific service planning and targeted resource allocation. Embedding IC screening within community platforms, with coordinated referral pathways, supports earlier identification and management of functional decline and advances...

Dietary protein quality, not merely quantity, shapes metabolic health and aging trajectories. Fanti et al. show that moderate methionine supplementation to a low-protein, Mediterranean-inspired diet activates a GH-GLP-1-FGF21 axis that reduces adiposity and frailty without caloric restriction; their findings provide a mechanism for why traditional plant-rich diets may promote longevity while sometimes compromising physical robustness.

The spleen harbors distinct macrophage subsets that support circulatory homeostasis and initiate immune responses, but the ontogeny and long-term dynamics of these populations remain incompletely understood. Here, we identified a transcriptionally and developmentally distinct CD163-expressing red pulp macrophage (CD163^(high) RPM) population that arose from yolk sac progenitors and occupied a vascular-associated niche. Using fate-mapping models, we showed that CD163^(-) RPMs were progressively...

Alzheimer's disease (AD), as the leading cause of dementia, poses an increasingly severe socioeconomic burden in the context of global ageing. Traditionally defined by amyloid-β and tau pathology, it's increasingly recognized as a systems disorder in which impaired glucose metabolism, mitochondrial dysfunction, and neuroinflammation interact across neural cell types and disease stages. However, the interaction among these three mechanisms, their role in promoting the classical pathology of AD,...

Bilingualism offers a powerful test case for understanding how control systems adapt to sustained, variable attentional demands. Converging evidence across behavioral, structural, functional, and clinical literatures indicates that repeated demands for selection, conflict resolution, and language switching are associated with reorganization of control architecture in ways that are consistent with predictive and reinforcement-learning mechanisms, producing two interdependent outcomes. Efficiency...

INTRODUCTION: Aging is associated with impaired skeletal muscle mass and function, often attributed to reduced sensitivity to anabolic stimuli. This study investigated whether aging influences the sensitivity of key anabolic signaling pathways to mechanical tension development in skeletal muscle.

CONCLUSION: Dual assessment of olfaction and gustation may represent a promising candidate biomarker of neurodegenerative progression compared to isolated olfactory testing. We propose the integration of standardized chemosensory protocols into routine geriatric assessments as a pragmatic strategy for early cognitive risk stratification and follow-up. This approach holds significant translational potential for monitoring neurodegenerative trajectories in older adults.

CONCLUSION: These results suggest that middle age may represent a critical transition stage preceding neuroinflammation and neurodegeneration, making it an attractive window to identify preventive or therapeutic targets in early AD. Collectively, this study identifies candidate pathways and genes that warrant further experimental validation in the context of AD and age-related neurodegeneration.

CONCLUSIONS: Results suggest that both the 10RM and 15RM RT protocols significantly increase estimated SMM in older women, with no significant differences between training conditions. Although substantial interindividual variability in adaptive responses exists, training load intensity does not appear to meaningfully influence responsiveness status in most individuals. These findings suggest that both loading schemes can be effectively prescribed to promote SMM gains in older women.

Excess sugar consumption is implicated in multiple cancers through insulin resistance, chronic inflammation, and metabolic reprogramming, yet whether early-life sugar exposure causally shapes long-term cancer risk remains an open question. We exploit the abrupt end of United Kingdom sugar rationing in September 1953 as a natural experiment, analyzing 64,761 UK Biobank participants born 1951-1956. Cohorts whose first 1,000 d of life fell under rationing exhibit dose-dependent reductions in adult...

Various cellular stressors inhibit translation initiation and promote ribosome disassembly, thereby transiently inducing stress granules (SGs), dynamic ribonucleoprotein condensates that contain mRNAs and RNA-binding proteins. Although SG assembly is usually reversible, dysregulated SG dynamics can trigger the formation of persistent ubiquitin-positive protein inclusions. There is increasing evidence that this conversion of SGs into insoluble aggregates represents a central pathogenic mechanism...

Epigenetic aging clocks based on DNA methylation patterns across the genome have emerged as a potential biomarker for risk of age-related diseases, like Alzheimer's disease (AD), and environmental and social stressors. However, methylation clocks have not been comprehensively validated in genetically diverse individuals. Here, we evaluate a set of first-, second-, and third-generation methylation clocks in 621 AD patients and matched controls from African American, Hispanic, and White cohorts....

During myogenic differentiation, the cellular architecture and proteome of muscle stem cells and myoblasts undergo extensive remodeling. These processes are partially understood and display alterations in disease and aging, resulting in impaired regeneration. Here, we used mass spectrometry to quantify the temporal dynamics of over 6000 proteins during myogenic differentiation. We identified the actin nucleator leiomodin 1 (LMOD1) among a restricted subset of cytoskeletal proteins increasing in...

Intrinsic capacity (IC) reflects multidomain functional reserve and a measurable phenotype of healthy ageing, but its biological correlates remain incompletely understood. We examined associations of neurofilament light chain (NfL), CXCL9 and inflammatory biomarkers with IC in community-dwelling older adults. We conducted a cross-sectional analysis within the Screening and Prevention of Intrinsic Capacity Decline in Elders (SPICE) programme. IC was derived from locomotion (SPPB), cognition...

Brain MRI shows promise for predicting cognitive functioning, but its utility depends on its capacity to capture stable between-person differences (e.g., patient stratification), longitudinal within-person changes (e.g., prognosis, treatment monitoring), or both. Using longitudinal data from 450 adults (aged 21-90; up to three waves, five years apart) in the Dallas Lifespan Brain Study, we benchmarked five modalities, task fMRI, functional connectivity (FC), structural MRI (sMRI),...