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BACKGROUND: Alzheimer's disease neuropathology, characterised by amyloid β (Aβ) and phosphorylated-tau (p-tau) protein accumulation, has primarily been assessed with biomarkers in clinical samples of older adults. Less is known about plasma biomarkers of Alzheimer's disease neuropathology and their associations with cognitive outcomes in midlife in diverse community-based samples. Our goal was to address these gaps.

BACKGROUND: Tau PET imaging has emerged as a critical biomarker for Alzheimer's disease, informing diagnosis, staging, and therapeutic selection. We investigated whether PET tracer selection alters tau detection.

BACKGROUND: Prasinezumab has previously shown potential for reducing the progression of motor signs (Movement Disorder Society-sponsored Revision of the Unified Parkinson's Disease Rating Scale [MDS-UPDRS] Part III) in patients with early-stage Parkinson's disease who were treatment-naive or receiving monoamine oxidase type B (MAO-B) inhibitors. The aim of the PADOVA trial was to evaluate the efficacy and safety of prasinezumab in a broader population of patients receiving stable symptomatic...

Alzheimer's disease is the leading cause of dementia and among the top ten leading causes of death in high-income countries. Exponential advances in epidemiology, genetics, diagnostic imaging and fluid biomarkers, treatment, and prevention in the last decade reinforce the notion that we are entering a new era in the clinical management of Alzheimer's disease. However, far from triumphalism, this momentum should be accelerated to achieve the goals of preventing Alzheimer's disease and arresting...

Transposable elements (TEs) are implicated in aging and neurodegenerative disorders, but the impact on brain TE RNA dynamics in these phenomena is not fully understood. Therefore, we quantify TE RNA changes in aging postmortem human and mouse brains and in the neurodegenerative disorders Huntington's disease (HD) and Parkinson's disease (PD). We track TE small RNAs (smRNAs) to assess the relationship to TE large RNA (laRNA) expression patterns. Human brain transcriptomes from the BrainSpan Atlas...

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Chaperone-mediated autophagy (CMA) is a selective lysosomal pathway essential for proteostasis and stress adaptation that declines with aging and metabolic disease, conditions closely linked to hepatocellular carcinoma (HCC). Using genetically engineered mouse models with systemic, hepatocyte-specific, or T cell-specific deletion of the CMA regulator LAMP2A in an MYC-driven, TP53-deficient HCC context, we demonstrate that CMA exerts cell-type-dependent tumor-suppressive functions....

Speaking more than one language is hypothesized to lead to greater brain resilience in aging and Alzheimer's disease, resulting in a delay in the symptom onset of Alzheimer's disease. While previous research has used structural neuroimaging measures to explore the neural underpinnings of this protective effect, few studies have used functional brain measures. Thus, we used functional connectivity measures of resting-state fMRI data to explore the association between multilingualism and brain...

Aging is characterized by the loss of tissue homeostasis, traditionally captured by the hallmarks of aging, yet how these hallmarks integrate to drive organismal decline remains unresolved. We propose mesenchymal drift, a process in which cells progressively lose lineage identity and adopt mesenchymal features, as a convergent framework that integrates the hallmarks of aging. Accumulating evidence suggests that mesenchymal drift can both arise from and reinforce these hallmarks, forming a...

Glucocorticoids (GCs) are essential endocrine regulators coordinating stress responsiveness, metabolic flexibility, inflammatory resolution, and circadian physiology. While acute GC fluctuations are adaptive, sustained exposure (arising from psychosocial stress, circadian disruption, obesity, chronic inflammation, neoplasms, or steroid therapy) elicits pleiotropic effects that overlap with biological aging. Prolonged GC signaling intersects with multiple hallmarks of aging by altering nutrient...

BACKGROUND: Alzheimer's disease neuropathology, characterised by amyloid β (Aβ) and phosphorylated-tau (p-tau) protein accumulation, has primarily been assessed with biomarkers in clinical samples of older adults. Less is known about plasma biomarkers of Alzheimer's disease neuropathology and their associations with cognitive outcomes in midlife in diverse community-based samples. Our goal was to address these gaps.

BACKGROUND: Tau PET imaging has emerged as a critical biomarker for Alzheimer's disease, informing diagnosis, staging, and therapeutic selection. We investigated whether PET tracer selection alters tau detection.

Adipose tissue and skeletal muscle are metabolically active tissues that play a central role in whole-body energy homeostasis. The functionality of these tissues, and hence cardiometabolic health, relies on adequate adjustments in perfusion reflecting metabolic demands in different physiological conditions. Acute exercise increases skeletal muscle perfusion, and this response can be enhanced by prolonged exercise training. Yet, whether similar responses occur in adipose tissue remains unclear....

Transposable elements (TEs) are implicated in aging and neurodegenerative disorders, but the impact on brain TE RNA dynamics in these phenomena is not fully understood. Therefore, we quantify TE RNA changes in aging postmortem human and mouse brains and in the neurodegenerative disorders Huntington's disease (HD) and Parkinson's disease (PD). We track TE small RNAs (smRNAs) to assess the relationship to TE large RNA (laRNA) expression patterns. Human brain transcriptomes from the BrainSpan Atlas...

Pulmonary aging is characterized by progressive structural and functional decline. Neddylation is recognized as a crucial mechanism for maintaining cellular homeostasis; however, its function in pulmonary aging has not been fully elucidated. In this study, we found that the core neddylation E2 enzyme UBE2M was downregulated in aged lung tissues. Ube2m knockdown mice exhibited premature pulmonary aging, including vascular degeneration and structural disruption. Notably, in the lungs of knockout...

Natural killer/T-cell lymphoma (NKTCL) is an aggressive haematological malignancy with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. The mechanisms underlying multidrug resistance in NKTCL remain unclear and present an urgent challenge that must be addressed during clinical treatment. Multidrug-resistant NKTCL models were established using adriamycin (ADM), and cellular senescence was confirmed by markers including P16, P21, and senescence-associated...

Mitochondria are increasingly recognized as master regulators of aging, integrating bioenergetics, redox control, stem cell fate, and innate immune signaling. This review synthesizes evidence that mitochondrial dysfunction is not only a hallmark but also an upstream driver of stem cell exhaustion and inflammaging. We discuss how age-associated mitochondrial DNA (mtDNA) mutations and clonal mosaicism impair respiration and reshape metabolite availability, thereby reprogramming long-lived...