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A new study probes consciousness with models that simulate and classify brain activity. A neuroscientist behind the work explains its ambitions

Alzheimer's disease (AD) is a highly prevalent progressive neurodegenerative disorder with unclear etiology, complex symptoms, and limited treatment options. Early pathological processes in AD emerge long before the onset of overt cognitive and motor symptoms and involve the accumulation of amyloid-β oligomers and neurofibrillary tangles, accompanied by neuroinflammation and neuronal loss. Importantly, the brain reward system comprises cortical and subcortical structures that share neurochemical...

Neurodegenerative diseases (NDs) pose clinical challenges due to their complexity and molecular heterogeneity. Here, we present a pan-neurodegeneration atlas (PanNDA) from multilayer, deep proteomic analysis of 2,279 human brain samples spanning 6 major NDs: Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal lobar degeneration with TDP-43 pathology, progressive supranuclear palsy with tau pathology, vascular dementia, and Parkinson's disease. PanNDA integrates data from whole...

Alterations to the protein and microRNA cargo of extracellular vesicles (EVs) occur in Alzheimer's disease (AD) and may contribute to disease progression. We previously showed that ingestion of amyloid-beta (Aβ) by both murine and human astrocytes leads to alterations to the protein cargo of EVs that induce significant neuronal impairment and apoptosis. Here, we hypothesised that pathological changes to the microRNA cargo of astrocyte-derived EVs (ADEVs) would also occur following exposure of...

β-Amyloid (Aβ) and tau pathologies are hallmark lesions of Alzheimer's disease (AD) and they develop in human brain following differential spatiotemporal trajectories. Accordingly, young/adult-onset tau-independent β-amyloidosis is rare. We encountered four such cases among 397 banked brains, with the donors died of hematological malignances (blood cancers) or cardiovascular diseases. To explore the pathological implication, we examined 17 brains (10-87 year-old, y) from blood cancer patients...

Accurate age estimation is key to understanding life history, population ecology, and effective management of valuable commercial and ecologically relevant species. While DNA methylation-based epigenetic clocks are well developed in mammals, their application in fish is limited. In contrast to mammals, fish lack identified universal fish epigenetic markers. Here we explore the potential of ultra-conserved elements (UCEs) as age predictor markers in albacore tuna (Thunnus alalunga), a worldwide...

In a little over 100 years, global life expectancy has increased by ∼60%. Paradoxically, it has been estimated that we now exercise five times less than we did 100 years ago. Despite a marked increase in life expectancy, the prevalence of non-contagious diseases (NCDs), otherwise known as "chronic lifestyle diseases," such as cardiovascular disease, type 2 diabetes, cognitive diseases, and cancer, has increased. Here, we discuss the concept of "exercise as medicine" for the treatment of NCD and...

DNA damage and mutations in hematopoietic stem cells (HSCs) enable clonal hematopoiesis (CH). Such damage occurs across a lifetime, but its origins remain unknown. Here, we demonstrate that endogenous formaldehyde causes HSC attrition and subsequently CH. We generated conditional mouse models lacking formaldehyde detoxification and Fanconi anemia (FA) DNA repair in blood. Formaldehyde protection was crucial for embryonic HSC emergence and throughout life. Despite severe deficiencies in HSCs,...

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Cataract is a leading cause of visual impairment worldwide, and its prevalence is increasing with population aging. The majority are age-related cataracts (ARC), clinically classified into nuclear, cortical, and posterior subcapsular cataracts (PSC) by opacity location. Mechanisms of cataractogenesis remain incompletely understood. While cortical and nuclear cataracts are largely attributed to crystallin aggregation, such protein-centric mechanisms fail to explain the early onset and axial...

CONCLUSION: Neighbourhoods play a crucial role in supporting older adults' flourishing, but evidence on causal pathways and life-course dynamics remains limited. The proposed integrative framework enhances conceptual clarity and provides a foundation for longitudinal research to guide place-based interventions for positive ageing.

With age, human skin undergoes a progressive decline in essential functions, including barrier protection, immunity, and wound healing capacity, which underlie many age-related skin diseases. Skin aging is not only driven by chronological aging, but also strongly influenced by extrinsic stressors, notably ultraviolet radiation, pollutants, and diet. Thus, understanding the complex interplay between these intrinsic and extrinsic factors is essential for developing strategies to preserve skin...

Frailty is an established benchmark of aging-related decline, yet most measures of frailty focus on physical decline. Increasing evidence that social environments influence trajectories of aging has led to growing interest in social frailty. Recently, a 10-item Social Frailty Index (SFI-10) was developed using data from the Health and Retirement Study (HRS) that used 8 social items plus chronological age and sex to predict mortality. This study evaluates the validity of the SFI-10, providing...

Interorgan communication is essential for metabolic homeostasis and healthy aging, with adipose tissue acting as a central hub that coordinates systemic metabolism, stress responses, and longevity. Here, we show that the miRNA-processing enzyme Dicer-1 (Dcr-1) acts in the fat body (FB) to regulate Dilp2 secretion from brain insulin-producing cells (IPCs), thereby modulating systemic insulin signaling and lifespan in Drosophila. Dcr-1 expression is reduced in multiple long-lived conditions, and...

Aging is a major contributor to the escalating prevalence of heart failure (HF). Ferroptosis has been implicated in age-related disorders and cardiovascular diseases. The role of ferroptosis in age-related HF remains unclear. Here, we show that aged rats exhibit impaired cardiac function accompanied by hallmark features of ferroptosis, including reduced glutathione peroxidase 4 (GPX4) expression and excessive lipid peroxidation. Consistently, cardiomyocyte-specific GPX4 knockout mice develop...

Cancer is associated with biological aging and functional decline; however, few studies have simultaneously examined objective changes in physical function and biological aging in older adults who develop cancer. We therefore compared functional and accelerated aging in generally healthy adults with and without incident invasive cancer, using data from DO-HEALTH, a three-year, randomized controlled trial including 2152 participants (mean age: 74.9 years, 61.1% women), free of major health...

Frailty is a modifiable aging-related condition driven by chronic inflammation and metabolic dysregulation, which are influenced by diet. Metabolomic profiling captures individual metabolic responses and can uncover mechanisms linking diet to frailty. This study examined the effects of food-derived metabolites on changes in frailty risk, both directly and through inflammatory pathways. This longitudinal study included baseline and three-year follow-up data from 9992 participants aged 45-85 years...

Older age combined with chronic disease increases the risk of malnutrition and frailty, impacting disease recovery and overall clinical outcomes. Serum concentrations of several trace elements and their respective biomarkers have not yet been investigated with regard to frailty in older adults with disease, although these patients most likely have an altered trace element profile owing to both inflammatory conditions and inadequate dietary intake. This cross-sectional study investigated trace...

Haematopoiesis has long been a paradigm for understanding how human genetic variation can influence physiology in health and disease, ranging from the genetic characterization of Mendelian blood diseases to population-scale genomic studies of blood cell phenotypes and diseases. More recently, advances in single-cell genomics and variant-to-function mapping are enabling mechanistic insights into how genetic variation shapes blood cell development. Alongside inherited variation, the...

How minute pathogenic signals trigger decisive immune responses is a fundamental question in biology. Classical signaling often relies on ATP-driven enzymatic cascades, but innate immunity frequently employs death fold domain (DFD) self-assembly. The energetic basis of this assembly is unknown. Here, we show that specific DFDs function as energy reservoirs through metastable supersaturation. Characterizing all 109 human DFDs, we identified sequence-encoded nucleation barriers specifically in the...