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Early sleep disruption is a hallmark of preclinical Alzheimer's disease (AD), but its underlying mechanisms are unclear. The locus coeruleus (LC) dopamine-β-hydroxylase noradrenergic (LC^(DBH)) neurons are vulnerable to early tau pathology in AD. Using P301S transgenic mice and cell-type-specific tau overexpression models, we show that pathological tau accumulation selectively increases the intrinsic excitability of LC^(DBH) neurons. Tau-induced neuronal hyperactivity disrupts sleep homeostasis,...

Hibernation demands rapid brain adaptations, involving cycles of reduced metabolic rate during torpor, followed by brief periods of arousal. Previous studies show hibernation induces a drastic increase in Tau hyperphosphorylation, but a mechanistic connection to disease remains unclear. Using single-nucleus RNA sequencing on hippocampi of golden hamsters, we unveil large transcriptional shifts across the hibernation cycle in all cell types, especially glia. Common transcriptional changes in...

Identifying the neurobiological basis of cognitive vulnerability is essential for preventing Alzheimer's disease (AD). We derived the Alzheimer's Resilience-Vulnerability Connectome (ARC) by contrasting SuperAgers (SA), an extreme phenotype of preserved late-life memory, with AD using resting-state fMRI. ARC distinguished SA from AD in a discovery cohort (N = 290; AUC = 0.85) and replicated independently (N = 143), involving prefrontal, temporal, and insular networks and associating with brain...

Early-onset Alzheimer's disease (EOAD) and late-onset AD (LOAD) differ in clinical presentations and rates of progression. We aimed to compare baseline and longitudinal tau positron emission tomography (PET) burden measured with ^(18)F-flortaucipir and its relationship with clinical variables in amyloid PET-positive, cognitively impaired participants from the Longitudinal Early-Onset Alzheimer's Disease Study (EOAD; n = 390) and Alzheimer's Disease Neuroimaging Initiative (LOAD; n = 211)....

Declining global fertility has produced a growing, often invisible population facing Elderly Companionship Collapse-older adults who are childless, kinless, sole family survivors, or aging solo. AI companions already simulate presence; Phase II avatars that digitally resurrect deceased loved ones are now feasible. This prospect offers solace but risks a "perfection trap" that could incentivize replacing human partners, and ontological confusion by blurring the boundary between life and death. We...

Companion dogs are a valuable source of translational discovery about the basic biology of aging because of their well-characterized genome, phenotypic variation in lifespan, aging, and disease profiles, and diverse environmental exposures shared with their human owners. The Dog Aging Project (DAP)'s prospective, longitudinal open cohort study was begun in 2019 to investigate the biological and environmental determinants of healthy aging in companion dogs. As of December 31, 2024, the study has...

Age-related loss of muscle and bone mass and increased adiposity contribute to frailty, disability, falls, and fractures. The hallmarks of aging framework provide a biological model to investigate mechanisms underlying body composition remodeling. However, whether hallmark-related biomarkers are associated with longitudinal body composition changes remains unclear. We conducted a narrative review of longitudinal human studies examining associations between biomarkers and body composition...

CONCLUSIONS: In this cross-sectional study, lower cognitive performance in PD was more strongly associated with age at assessment and its interaction with disease severity than with age at onset. Education and cognitive reserve were positively associated with cognitive performance, consistent with their protective role.

Aging impairs organ regeneration, with insufficient angiogenesis as a key contributor. Here, we show that the endothelial immunoproteasome subunit PSMB8 is upregulated in aged mouse livers after partial hepatectomy. Endothelial PSMB8 deletion or PR-957 inhibition promotes angiogenesis and rescues liver regeneration. diGly proteomics identifies TAZ (transcriptional co-activator with PDZ-binding motif) as a ubiquitin-dependent immunoproteasome substrate, and TAZ activation restores aged liver...

Glaucoma, a leading cause of irreversible blindness, involves progressive retinal ganglion cell loss. Early detection of this neurodegeneration is critical, yet current clinical methods often identify disease only after substantial damage has occurred. This preliminary study used high-resolution adaptive optics-optical coherence tomography (AO-OCT) to track individual retinal ganglion cells in patients and healthy volunteers over 3 to 5 years. Results revealed higher neurodegeneration in...

Identifying the neurobiological basis of cognitive vulnerability is essential for preventing Alzheimer's disease (AD). We derived the Alzheimer's Resilience-Vulnerability Connectome (ARC) by contrasting SuperAgers (SA), an extreme phenotype of preserved late-life memory, with AD using resting-state fMRI. ARC distinguished SA from AD in a discovery cohort (N = 290; AUC = 0.85) and replicated independently (N = 143), involving prefrontal, temporal, and insular networks and associating with brain...

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Bone marrow (BM) adiposity changes radically through the lifespan, but this phenomenon is poorly characterized and understood in humans. Large datasets of magnetic resonance imaging (MRI) scans of the head have been collected to study the human brain, but also contain unexploited information about other organs. We developed an artificial neural network that localizes calvarial BM in T1-weighted MRI head scans, enabling us to study its composition in several large MRI datasets, and to model...

Skeletons across Europe confirm the Goths surged out of Scandinavia before sacking Rome

Model of the telescope’s imperfections helps strip away starlight obscuring faint exoplanets

Aging selectively degrades neuronal structure and function, yet the signals that actively preserve neuronal integrity over adult life remain incompletely defined. In Caenorhabditis elegans, the PVD sensory neuron develops progressive excessive higher-order dendritic branching during normal aging that correlates with declines in proprioceptive locomotion. Using this system as a quantitative in vivo readout of neuronal healthspan, we identify the cholecystokinin-like neuropeptide NLP-12 as a...

DNA double-strand breaks (DSBs) are the most genotoxic form of DNA damage. Unrepaired DSBs may cause loss of chromosome fragments at mitosis, while incorrectly repaired DSBs can cause chromosome aberrations and other adverse effects, leading to cell cycle arrest, senescence, cell death, or neoplastic transformation. Detecting and quantifying DSBs is important in studies of genome instability, aging, and cancer. Methods of detecting and quantifying DSBs fall into two broad categories:...

Bone marrow (BM) adiposity changes radically through the lifespan, but this phenomenon is poorly characterized and understood in humans. Large datasets of magnetic resonance imaging (MRI) scans of the head have been collected to study the human brain, but also contain unexploited information about other organs. We developed an artificial neural network that localizes calvarial BM in T1-weighted MRI head scans, enabling us to study its composition in several large MRI datasets, and to model...

PHB2 (prohibitin 2), a well-known inner mitochondrial membrane mitophagy receptor, has recently emerged as a potential sensor of intracellular bacteria. A recent study shows that increased exposure of the inner mitochondrial membrane protein PHB2 enables its interaction with bacterial surface proteins and the recruitment of the E3 ubiquitin ligases ARIH1 (ariadne RBR E3 ubiquitin protein ligase 1) or PRKN (parkin RBR E3 ubiquitin protein ligase), thereby promoting xenophagy. This finding expands...

BackgroundParental longevity is linked to better offspring cognition, with limited evidence from middle-income countries. We examined associations between parental longevity and cognition in Mexico while controlling for health, socioeconomic status (SES), and genetic factors.MethodsWe used the 2018 wave of the Mexican Health and Aging Study (n = 5,049; age 65+). Maternal/paternal longevity was based on survival to age 85 or older. We used latent variable regressions to estimate associations with...