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The nucleus basalis of Meynert (nbM), the major cholinergic output of the basal forebrain, regulates cortical modulation, learning, and memory. Dysfunction of the nbM-cortical cholinergic pathway is implicated in neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease (AD) and Down syndrome (DS). Here, we generated human nbM organoids (hnbMOs) from human pluripotent stem cells (hPSCs) containing functional cholinergic projection neurons. Then we reconstructed...

The corpus callosum (CC) is the largest set of white matter fibers connecting the two hemispheres of the brain. In humans, it is essential for coordinating sensorimotor responses and performing associative or executive functions. Identifying which genetic variants underpin CC morphometry can provide molecular insights into the CC's role in mediating cognitive processes. We developed and used an artificial intelligence based tool to extract the midsagittal CC's total and regional area and...

Senescence has been demonstrated to either inhibit or promote tumorigenesis. Resolving this paradox requires spatial mapping and functional characterization of senescent cells in the native tumor niche. Here, we identify p16^(Ink4a)+ cancer-associated fibroblasts enriched with senescent phenotypes that promote fatty acid uptake and utilization by aggressive lung adenocarcinoma (LUAD) driven by Kras and p53 mutations. Furthermore, rewiring of lung cancer metabolism by p16^(Ink4a)+...

To meet the challenge of wintering in place, many high-latitude small mammals reduce energy demands through hibernation. In contrast, short-lived Eurasian common shrews, Sorex araneus, remain active and shrink, including energy-intensive organs in winter, regrowing in spring in an evolved strategy called Dehnel's phenomenon. How this size change is linked to metabolic and regulatory changes to sustain their high metabolism is unknown. We analyzed metabolic, proteomic, and gene expression...

Multimorbidity is projected to continue increasing in England and many other countries. Here, we use a validated microsimulation model to quantify the potential impact of improving exposure levels of eight risk factors on the burden of major illness among adults aged 30+ in England between 2023-2043. We find that the biggest contributors to incident major illness are body mass index, smoking, systolic blood pressure, and physical inactivity. Theoretical minimum risk exposure levels of all risk...

Symbiotic nitrogen fixation (SNF) in legume-rhizobia represents a sustainable and eco-friendly alternative to chemical nitrogen fertilizers in agriculture. Identifying key factors involved in nodule senescence, is crucial for enhancing SNF by effectively extending the lifespan of nodules. Here, we reveal that sulfur (S), an essential element for SNF, plays a major regulatory role in the senescence of soybean (Glycine max) nodules. Blocking S input into the symbiosome by knocking out either S...

Chromosome mis-segregation during meiosis in oocytes causes miscarriages and congenital diseases. Ageing-associated premature chromosome separation is a major cause of mis-segregation. Effective prevention of premature chromosome separation has not yet been achieved. Here we design protein-based artificial kinetochores that act as decoys to prevent premature chromosome separation. Designed artificial kinetochore-like decoys are submicroscale clusters of NDC80-NUF2-tethered protein particles that...

Across species, a major axis of variation in social behaviour relates to how offspring are reared. Parental care behaviours have independently evolved in hundreds of animal lineages. Care is usually limited to one or both parents, but in some lineages parenting is a highly cooperative endeavour. In social insects, for example, entire societies have evolved around parenting, complete with distinct adult morphs that specialize in reproduction, nursing, foraging and defence. Recent advances in omic...

Aging is associated with increased breast cancer risk, and the oldest and youngest patients have worse outcomes, irrespective of subtype. It is unknown how age affects cells in the breast tumor microenvironment or how they contribute to age-related pathology. Here we discover age-associated differences in cell states in human estrogen receptor-positive and triple-negative breast cancers using analyses of existing bulk and single-cell transcriptomic data. We generate and apply an Age-Specific...

Most cancers are diagnosed in people over 60 years of age, but little is known about how age impacts tumorigenesis. While aging is accompanied by mutation accumulation (widely understood to contribute to cancer risk) it is associated with numerous other cellular and molecular changes likely to impact tumorigenesis. Moreover, cancer incidence decreases in the oldest part of the population, suggesting that very old age may reduce carcinogenesis. Here we show that aging represses oncogenic...

Aging biomarkers are essential tools for quantifying biological aging, but systematic validation has been hindered by methodological inconsistencies and fragmented datasets. Here we show that the ability of traditional aging clocks to predict chronological age does not correlate with mortality prediction capacity (R = 0.12, P = 0.67), suggesting that these metrics capture distinct biological processes. We developed Biolearn, an open-source framework enabling standardized evaluation of 39...

The Asian Working Group for Sarcopenia (AWGS) presents an updated 2025 consensus reframing sarcopenia management through a life-course approach to muscle health promotion. While aligning with the Global Leadership Initiative in Sarcopenia (GLIS), this update provides healthcare providers with Asia-specific guidance. The consensus introduces three key refinements: first, expanding sarcopenia diagnosis to middle-aged adults (50‒64 years) with validated diagnostic thresholds; second, simplifying...

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Neurodegenerative disorders alter mitochondrial functions, including the production of reactive oxygen species (ROS). Mitochondrial complex III (CIII) generates ROS implicated in redox signalling, but its triggers, temporal dynamics, targets and disease relevance are not clear. Here, using site-selective suppressors and genetic manipulations together with live mitochondrial ROS imaging and multiomic profiling, we show that CIII is a dominant source of ROS production in astrocytes exposed to...

CONCLUSION: Against our hypothesis, the present pilot study indicated that neither a 12-week MMI nor UMI seems to have a sizable impact on gait parameters and cognitive performance in physically active healthy adults. Still, a significant increase in the external load used during resistance training was observed, implying neuromuscular adaptations, which, however, did not translate into a higher gait and/or cognitive performance.

CONCLUSION: This study observed distinct trajectories of care expenditure among older people at the end-of-life and multiple factors contributed to these patterns. Most followed a trajectory where both where health and social expenditure remained high and persons relied on care in their own homes. These findings provide insight into the care resources used during the last year of life and may serve to inform future policies on care planning in the context of an ageing population.

Emerging clinical evidence suggests a link between environmental noise and the severity of Parkinson's disease (PD). However, the effects of high-decibel noise exposure on PD and its underlying mechanisms remain unclear. In this study, we demonstrate that acute noise exposure induces reversible motor deficits in subacute low-dose 6-hydroxydopamine (6-OHDA) mice, a model of presymptomatic early-stage PD, while chronic noise exposure results in irreversible motor deficits and significant loss of...

Aging is a predominant risk factor for heart disease. Aging heart reveals low-grade chronic inflammation, cell apoptosis, cardiac fibrosis, and increased vulnerability to ischemic injury. The underlying molecular mechanisms responsible for cardiac aging and its susceptibility to injury are not fully understood. Although literature reports a role for mitochondrial Arginase 2 (ARG2) in heart failure, contradictory results are reported. How ARG2 participates in cardiac aging is still unknown. In...

Alzheimer's disease (AD), the leading cause of dementia, could potentially be mitigated through early detection and interventions. However, it remains challenging to assess subtle cognitive changes in the early AD continuum. Computational modeling is a promising approach to explain a generative process underlying subtle behavioral changes with a number of putative variables. Nonetheless, internal models of the patient remain underexplored in AD. Determining the states of an internal model...

Blue Skies Space will sell data from its tiny, low-cost UV telescope