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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...

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide and the leading cause of dementia in older adults. The presence of extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) constitutes the two principal neuropathological features of AD. However, current therapies targeting only Aβ or tau remain suboptimal, likely due to intrinsic neuronal and glial dysfunction in affected brain regions. Urolithin A (UroA) is a widely recognized...

Synaptic dysfunction emerges early in Alzheimer's disease, often years before the appearance of clinical symptoms, and is among the most reliable predictors of subsequent cognitive decline. Despite its importance, the cellular events that trigger this early synaptic vulnerability remain poorly defined. Growing evidence points to a critical failure at the interface between neuronal energy metabolism and synaptic signalling, commonly referred to as the mitochondria-synapse axis, suggesting that...

A growing body of research is focusing on how music, technology, and neuroscience can converge to promote healthy ageing and counteract pathological decline. In particular, music interventions for older adults have been garnering increasing attention, with numerous reports showing positive effects of music on various health outcomes, including psychological well-being, cognitive function, physiological responses, quality of life, and overall well-being. In this context, the European...

Human aging is characterized by complex structural and functional decline, but quantifying its heterogeneity and assessing biological age remain challenges. We present the mCAS (multicentric Chinese aging standardized cohort) developed from 2,019 Chinese individuals aged 18-91 years. Integrating high-dimensional clinical, physiological, and molecular-level data, we constructed a three-tiered aging framework: the core capacity clock (CC-clock) to quantify clinical physiological decline, the...

CONCLUSIONS: These results suggest that even decline confined to a single physical performance domain may signal an early transition toward increased vulnerability. Monitoring trajectories of physical performance may therefore help identify older adults at increased mortality risk before more widespread functional deterioration becomes apparent.

Descendants of longevity-enriched sibships demonstrate a broad health and survival advantage throughout the life course. However, little is known about manifestations during very early life. Here we show a pattern of lower risk of adverse early-life outcomes in third-generation grandchildren (N = 5637) of Danish longevity-enriched sibships compared to the general population, including infant mortality (Hazard Ratio = 0.53, 95% CI [0.36, 0.77]) and a range of neonatal health indicators. These...

sc-ChromAging, a chromatin accessibility-based aging clock, was developed using single-cell ATAC-seq from 401 Chinese individuals. It identified CD4⁺ naive T cells as the most accurate predictors of age. This clock linked immune aging with pathways in inflammation, infection, and tumor susceptibility, and connecting chromatin changes to plasma metabolites like triacylglycerols.

Move comes after Roger Innes complained about the government’s prosecution of Chinese postdocs

Cables used to detect earthquakes can also capture the faint vibrations of speech

In a recent study in Science, Chen et al. engineer astrocytes with anti-amyloid chimeric antigen receptors (CARs) to enable sustained, antigen-directed clearance of amyloid-β (Aβ) in vivo, revealing how CAR design can shape both pathology and glial responses.

Lipid homeostasis is essential for preserving the structural integrity and functional capacity of the brain. A diverse array of lipids, including cholesterol, phospholipids, and sphingolipids, has been identified as playing pivotal roles. Dysregulation of lipid metabolism is increasingly recognized as a central pathological mechanism in neurodegenerative diseases, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Cerebrotendinous...

Genome-wide association studies (GWAS) have identified APOE2 allele as linked to exceptional longevity, with carriers exhibiting a reduced risk of Alzheimer's disease (AD). Apolipoprotein E (APOE), a glycoprotein involved in lipid transport, has three major alleles. However, alterations in lipid metabolism alone do not fully explain APOE2's protective effects. In contrast, APOE4 is the strongest genetic risk factor for AD. To investigate how APOE2 promotes neuronal longevity and confers...

Trehalase, the primary enzyme responsible for the degradation of gastrointestinal trehalose ("mushroom sugar"), is well-characterised in the human gut, but has not been conclusively identified in the human brain. Trehalose itself has shown promise in neuroprotection through diverse molecular mechanisms, including the autophagy-driven clearance of cellular debris and neurotoxic aggregates. However, the mechanisms activating trehalose and its integration into human central nervous system processes...

Inter-organ communication plays a critical role in mammalian aging and longevity control. Here, we identified Mimecan from transcriptomic comparisons between young and aged skeletal muscles. Skeletal muscle-derived Mimecan regulates core body temperature via brown adipose tissue (BAT), which is impaired in aged mice. Skeletal muscle-specific loss- and gain-of-function models demonstrate that Mimecan activates melanocortin 4 receptor (MC4R)-positive neurons in the dorsomedial hypothalamus (DMH)...