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Parkinson disease (PD), the second most common neurodegenerative disorder, is pathologically linked to dysregulated autophagy, a conserved lysosomal degradation pathway. Current conventional PD therapies are often limited by significant side effects, underscoring the demand for alternative treatment strategies. Drug repurposing of FDA-approved compounds represents a promising approach to address this unmet clinical need. Here, by integrating clinical data analysis, we identified an association...

Cognitive dysfunction is an increasingly recognized complication of diabetes, contributing substantially to morbidity in the aging population, yet disease-modifying therapies remain scarce. Dietary intervention, a cornerstone of diabetes management, may offer neuroprotective potential. Low-carbohydrate ketogenic diets (LCKDs), typically restricting carbohydrates to < 50 g/day, effectively improve glycemic control and metabolic health. Emerging preclinical and clinical evidence suggests that...

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Aging is characterized by progressive loss of physiological resilience accompanied by increased susceptibility to chronic diseases. Among the interconnected hallmarks of aging, cellular senescence has emerged as a central driver of systemic inflammation through the senescence-associated secretory phenotype (SASP). Senescent cells accumulate across multiple tissues with advancing age and secrete complex mixtures of cytokines, growth factors, and proteases that reshape tissue microenvironments and...

Heart failure with preserved ejection fraction (HFpEF) is a cardiometabolic syndrome strongly associated with aging, systemic inflammation and endothelial dysfunction, in which impaired endothelial nitric oxide synthase (eNOS) signaling plays a central role. This study aimed to identify circulating proteins associated with HFpEF and to explore their relationship with endothelial alterations under metabolic stress. A total of 109 HFpEF patients and 49 control subjects underwent clinical,...

CONCLUSIONS: Perceived age-based discrimination is associated with increased healthcare utilization among older adults in India through both direct and indirect pathways, with the indirect effect operating via probable depression and subsequent multimorbidity. These findings highlight the importance of addressing discrimination and integrating mental health within primary care, while also accounting for rural-urban disparities, to promote equitable healthcare access and improve health outcomes...

Aging is a major independent risk factor for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, effective therapeutic strategies for this population remain limited. Here, we established a model of aging-associated MASLD by subjecting aged mice to a long-term high-fat diet (HFD), which recapitulated key disease features including progressive hepatic steatosis, inflammation, insulin resistance, and fibrosis. A 6-week exercise intervention...

FAM162A is an inner mitochondrial protein known for its role in hypoxia-induced apoptosis. However, it is often overexpressed in cancer, where its pro-apoptotic function appears to be overridden, suggesting novel unknown roles in mitochondrial function and cell survival. Furthermore, its precise localization, topology, and orientation remain controversial. In this study, we aimed to assess the role of FAM162A in mitochondrial structure, dynamics, and bioenergetics and its impact on cellular and...

CONCLUSIONS: These findings support the conclusion that somatic symptoms may disproportionately inflate depression scores among patients with ovarian cancer at diagnosis, which may potentially lead to misclassification or overestimation of depression severity. This highlights the need for refined measurement approaches that account for the somatic burden of cancer in assessing depression during active disease.

Interpreting genome-wide epigenomic experiments, such as DNA methylation profiling and chromatin accessibility assays, requires tools that can identify which regulatory programs underlie coordinated changes across genomic regions. Without this regulatory context, lists of differential regions remain largely descriptive and difficult to interpret mechanistically. Existing approaches either apply hard significance cutoffs that discard moderate but biologically meaningful signals, or rely on...

Bizarre injuries were not caused by sharks or boat propellers, but a more surprising culprit

Variability in Alzheimer's disease (AD) clinical presentation complicates mechanistic studies and therapeutic outcome prediction. Brain protein aggregate load does not directly correlate with clinical symptoms; however, different subtypes of AD have been reported to exhibit structural variation (polymorphism) of aggregates. Little is known about the structural diversity of the deposits in cognitively normal aged brains. This study investigates the structural heterogeneity of amyloid aggregates...

Nucleocytoplasmic transport is a central but underappreciated component of the proteostasis network as it controls the trafficking and partitioning of proteins between the nucleus and cytoplasm through the nuclear pore complex (NPC). Transport of large proteins across the NPC is mediated by karyopherins, a conserved family of importins and exportins that function through a Ran GTPase-dependent cycle. Beyond their canonical transport activities, karyopherins can directly contribute to...

Hypothesized to be a diet-derived 'longevity vitamin', Ergothioneine (ET) is increasingly recognized for its potential to modulate cellular homeostasis and support healthy ageing in preclinical models. This systematic review, encompassing evidence from 2005 to 2025, investigates ET's unique pharmacokinetics mediated by the OCTN1 (SLC22A4) transporter, which ensures its selective accumulation in tissues susceptible to age-related oxidative decline. Beyond its role as a secondary antioxidant...

Water diffusion gives rise to micron-scale sensitivity of diffusion MRI (dMRI) to cellular-level tissue structure. Precision medicine and quantitative imaging depend on uncovering the information content of dMRI and establishing its parsimonious hardware-independent fingerprint. Based on the rotational SO(3) symmetry, we study the geometry of the dMRI signal and the topology of its acquisition, identify irreducible components and a full set of invariants for the cumulant tensors, and relate them...

Macroautophagy/autophagy is a process conserved across eukaryotes that maintains cellular homeostasis by delivering cellular components to the vacuole or lysosome for further breakdown and recycling. Although the molecular mechanisms regulating autophagosome formation have been extensively studied, those underlying the modulation of autophagic body degradation in plant cells remain unclear. Here, we determined that VAB1 (V-ATPase catalytic subunit B1), a direct target of SINAT (SEVEN IN ABSENTIA...

Alzheimer's disease (AD) is associated with impaired connectivity in critical functional networks. This study investigated the effects of 20 Hz transcranial magnetic stimulation (TMS) on brain network mechanisms in 25 patients with AD, including 17 in the TMS group and 8 in the sham group. We analyzed resting-state functional magnetic resonance imaging data, using the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify neural activity and identify regions of...