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Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder with substantial heterogeneity in progression and treatment response. Despite recent therapeutic advances, predictive models capable of accurately forecasting individualized future biomarker states remain limited. Here, we present a machine learning-based operator learning framework for personalized modeling of AD progression, integrating longitudinal multimodal imaging, biomarker, and clinical data. Unlike...

Cardiac aging reduces stress resistance and increases the susceptibility to myocardial injury. Although cardiac dysfunction typically manifests in late-stage aging, the underlying process begins in middle age. Elevated endoplasmic reticulum (ER) stress is a key contributor to cardiac aging. We have shown that ER stress increases in middle-aged hearts and peaks in advanced age, while chronic metformin treatment reduces ER stress and improves mitochondrial function in late-aged hearts. This study...

Collagen, a central component of the extracellular matrix (ECM), precisely regulates tissue mechanical properties and biological functions through hierarchical assembly, playing a vital role in maintaining homeostasis. However, the molecular mechanism of assembly remains poorly understood, limiting insights into tissue remodeling, aging, and ECM-related diseases. Here, we employ time-resolved cryo-electron microscopy to resolve two critical hierarchical intermediates in fibrillar collagen...

Reactivating dead alkali metal is an effective strategy for extending the lifespan of alkali metal batteries. Until now, relevant works are mainly concentrated in lithium batteries, however, the reactivation of dead Na remains a mystery. Herein, dead Na reactivation is realized by a reverse-pulse-interspersed charging strategy. Transient large reverse currents are incorporated into the battery charging protocol, during which dead Na can be reactivated by the dielectrophoresis effect. Different...

The benefit of early diagnosis and treatment has been demonstrated in animal models of several lysosomal storage diseases. In a clinical setting, however, diagnoses are often not made until after patients become symptomatic. The lysosomal storage disease alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions throughout the brain and other tissues. In a feline model of alpha-mannosidosis, we previously...

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Methionine restriction has emerged as a promising strategy for extending lifespan and enhancing cancer therapy. LAT4, an amino acid transporter encoded by SLC43A2, is frequently overexpressed in multiple cancers and critically contributes to systemic methionine accumulation. However, the structural basis of LAT4 function remains poorly understood, and no effective inhibitors have been developed to date. In this study, we present high-resolution cryo-electron microscopy structures of LAT4 and the...

Photobiomodulation (PBM) is a non-invasive strategy to enhance cognitive function, yet the effects of stimulation frequency remain unclear. We applied pulsed 810 nm PBM at 5 Hz or 40 Hz to the frontal cortex of adult rats, and 40 Hz PBM to aged rats. In young adults, both stimulation frequencies enhanced cognitive flexibility, and in aged rats 40 Hz PBM improved learning speed. In terms of brain changes, we studied cytochrome c oxidase (CCO) activity, c-Fos expression and protein levels. We...

Small vessel disease and brain atrophy are linked to cognition in later life, but whether these associations persist in the oldest old is unclear, as lesion burden and survivorship may change effect sizes. We analyzed 249 adults aged 89-94 years from the Kawasaki Aging and Wellbeing Project. White matter hyperintensities (WMHs) were segmented on fluid-attenuated inversion recovery; gray and white matter volumes were derived from T1-weighted magnetic resonance imaging; and peak width of...

CONCLUSION: Falls are common among older adults in Ghana, with risk influenced by sex, residence, and functional status. Functional fitness plays a central role in fall risk, underscoring the value of targeted interventions to promote safe and healthy ageing in sub-Saharan Africa.

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Dopaminergic neurons are fundamental in governing motivation, movement, and many aspects of cognition. The targeted modulation of dopaminergic signaling serves as a cornerstone in developing therapeutic interventions for conditions such as Parkinson's disease, schizophrenia, and addiction. Despite the pivotal role of dopaminergic neurons, the ultrastructure of dopaminergic synapses remains poorly understood. Here, we establish and utilize a cryo-correlative light and electron microscopy process...

Age-related hearing loss (ARHL) is an increasingly common feature of aging and has been linked to poorer psychosocial wellbeing and increased dementia risk. Individuals with ARHL experience speech perception difficulties in noisy environments, wherein the brain must "turn up the volume" or upregulate neural activity to accurately parse speech from background noise. As the aging population steadily increases worldwide, it is essential to develop effective, non-invasive, and easily attainable...

Myofascial pain syndrome (MPS) in the elderly is a significant contributor to chronic pain and functional decline, driven by a unique set of age-related pathophysiological challenges. Core geroscience principles-including sarcopenia, inflammaging, and cellular senescence-converge to create a state of heightened central sensitization that amplifies pain. Traditional pharmacotherapy is fraught with risks in this population due to polypharmacy and vulnerability to adverse effects, with many common...

BACKGROUND: Sustained attention is a complex cognitive function required for the successful performance of tasks such as walking, cycling, driving, conversations and other prolonged tasks. Deficits of this function are associated with frailty, falls, and general cognitive decline in older adults. Sustained attention declines with age and is impaired in many neurological disorders. However, little is known about the underlying neurophysiological characteristics of sustained attention deficits in...

The association between aging and cancer has been extensively documented in observational studies, but their shared genetic basis remains unclear. Leveraging genome-wide association studies summary statistics of aging and pan-cancer (87,531 cases and 314,193 controls) within the European population, genetic correlation and Mendelian randomization analyses were used to estimate genetic correlations, and infer causal relationships between seven aging-related traits and pan-cancer. We further...

The microbiome is a key determinant of organismal health, yet inter-individual variability and heterogeneous responses to environmental conditions complicates the understanding of its effects on hosts. Here, we present a comprehensive analysis using the Drosophila Genetic Reference Panel (DGRP) to investigate how the interplay between host genetic variation and diet influences microbiome composition, and to assess whether microbiome features in young flies can be used to predict lifespan and...

The global demographic shift toward aging has precipitated a surge in age-related ocular pathologies, imposing a formidable public health challenge that demands urgent intervention. Blinding disorders such as age-related macular degeneration (AMD), cataracts, and dry eye disease exemplify this crisis, with their pathogenesis being intrinsically linked to tissue-specific aging processes in the eye. At the molecular level, core pathways including telomere attrition, oxidative stress, cellular...