Aging & Longevity

CONCLUSION: LLM-derived mobility functional status assessment was associated with ED visits and hospitalization, but not with all-cause mortality after adjustment. Prospective validation and evaluation of incremental discrimination, calibration, and clinical utility are needed before clinical implementation.

The ability to initiate stepping promptly and accurately is critical for safe mobility in later life. Choice stepping reaction time (CSRT) is an independent predictor of recurrent falls in older adults and is often prolonged in dementia. Although the prefrontal cortex (PFC) is crucial for rapid response execution, existing studies primarily focus on regional activation, leaving the topological reorganization of prefrontal functional networks poorly understood. In this study, twenty-six healthy...

Alzheimer's disease (AD) biomarkers may be associated with decline in non-cognitive domains of intrinsic capacity (IC), but such evidence has not been synthesized. This narrative review, based on a structured PubMed search (last search: December 31, 2025), included 119 human studies examining associations of core AD biomarkers (e.g., amyloid-beta (Aβ) and tau protein) and biomarkers of non-specific processes involved in AD pathophysiology (including neurofilament light chain (NfL), glial...

CONCLUSION: Frailty in older adults with cancer is affected by multi-dimensional, complex determinants. Targeted screening and intervention strategies can be formulated upon identification of these factors to reduce frailty incidence and improve clinical prognosis.

Although women live longer, they paradoxically face heightened susceptibility to cognitive and systemic decline emerging in midlife-an underexplored transition from resilience to vulnerability. Here, we investigate biological processes associated with this female-biased vulnerability and their molecular regulation. Senescence-associated features were preferentially elevated in middle-aged females in human brain and spleen tissues, with similar changes in mice. In female mice, epigenetic...

Nuclear factor I (NFI) misexpressions in humans are associated with severe brain malformations, yet the underlying mechanisms remain poorly understood. Here, we show that NFIs regulate the broad lineage progression and lifespan of radial glial progenitors (RGPs), thereby bidirectionally controlling neocortical development. Human cerebral organoids carrying patient-mimicking NFI mutations exhibit expression-level-dependent bidirectional impairments in RGP temporal development, coinciding with...

Oligodendrocytes are a specialized class of glial cells responsible for myelination, which sustains central nervous system (CNS) function. Though long considered a passive and static cell, the oligodendrocyte is now recognized to actively support axonal energy demands through metabolic provision, modify neural signaling in response to environmental stimuli through adaptive myelination, and repair or regenerate myelin following injury. However, oligodendrocytes become dysfunctional in aging and...

Microglia, the brain's resident immune cells, rely on histone modifications and chromatin remodeling to sculpt their identity across the trajectory from development through aging. Recent studies have identified enhancer rewiring and metabolic-epigenetic coupling-exemplified by histone lactylation-as central drivers of microglial plasticity. Disruption of this regulatory balance drives the transition from homeostatic microglia toward disease-associated microglia (DAM) in Alzheimer's and...

Insecticide resistance poses a major challenge to global pest management, yet its cascading effects on ecological networks remain poorly understood. Here, we show that target-site-resistant herbivorous insects can accumulate unmetabolized insecticides and inadvertently function as "toxic prey," impairing the fitness of their natural enemies. Using neonicotinoid- and spinosyn-resistant Myzus persicae and genetically modified Drosophila melanogaster, we demonstrate that resistant hosts surviving...

As the most popular hole-selective materials in efficient p-i-n perovskite solar cells (PSCs), self-assembled monolayers (SAMs) still remain great challenges in long-term stability due to their frail construction and week bonding. To form a toughened donor-acceptor interface, here, we adopt an amine-rich cross-linking templates for SAM layer growth. The enhanced Coulombic interaction between polymer amines and SAMs promotes the formation of SAM growth networks, resulting in reduced...

Naïve T cells maintain quiescence yet must respond rapidly to antigens, but how they prime this capacity is unclear. We identify histone variant H2A.Z as a key regulator of an epigenetic training program that licenses quiescent naïve CD8^(+) T cells for future activation. H2A.Z deficiency disrupts naïve T cell homeostasis and effector responses. Multiomics reveals that H2A.Z is selectively deposited at oxidative phosphorylation (OXPHOS) gene promoters in quiescent naïve CD8^(+) T cells, priming...

Oxidative stress, iron dyshomeostasis, and chronic neuroinflammation are the principal mechanisms involved in the progression of central nervous system (CNS) disorders, which are a significant source of death and chronic disability worldwide. This review focuses on understanding the mechanistic relationship between ferroptosis and neuroinflammation in central nervous system (CNS) disorders, which involves the molecular mechanisms, their role in the pathogenesis of the disease, and therapeutic...

Frailty is a complex geriatric syndrome characterized by age-related declines in physiological function and cognitive reserve. To promote early prevention and intervention, minimally invasive and objective biomarkers that can detect frailty progression are required. We aimed to identify biomarkers associated with frailty progression and to elucidate their relevance to the Japanese version of the Cardiovascular Health Study (J-CHS) criteria, consist of five components (unintentional weight loss,...

Senescence is a key pathomechanism across chronic diseases but also highly heterogeneous. In this study, we demonstrate that high-content imaging and transcriptomics can jointly shed light on senescence in vitro, distinguishing replicative and chemically induced senescence, differentiating from quiescence and characterizing the senolytic response.

Age-related olfactory decline in humans is well-documented, yet the underlying peripheral neural mechanisms remain poorly understood. We investigated age-related olfactory decline across psychophysical, nasal mucosal, and central neural levels in 73 healthy adults across the lifespan. Participants underwent Sniffin' Sticks testing and simultaneous recordings of mucosal electro-olfactograms (EOG) and cerebral chemosensory event-related potentials (CERP) in response to olfactory and trigeminal...

Aging bridges pose significant risks to public safety. Although existing sensing technologies offer a potential solution for structural health monitoring, the high cost and complexity of installing and maintaining sensing systems have limited their scalability and long-term deployment. Here, we present a scalable and cost-effective approach that turns pre-existing telecommunication (telecom) fiber-optic cables into a dense array of dynamic strain sensors to continuously monitor bridges. Using...

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CONCLUSIONS: Higher activity levels and higher day-to-day morning activity variance measured over just two to three mornings differentiate those at higher risk of death and frailty decline, increasing the feasibility of using accelerometry as a digital frailty screening tool.

Interest in fasting-based diets to improve metabolic health is growing. Caloric restriction (CR) with one meal per day includes an extended fasting component that contributes to its metabolic and longevity benefits, yet the role of fasting within CR remains unclear. Here, we compare CR with a fasting-refeeding-fasting (FRF) regimen while controlling food intake and fasting duration. Changes in plasma insulin and free fatty acids, hepatic mTOR signaling and ketogenesis, metabolic rhythms, and...