Aging & Longevity

Ageing is characterised by the coupled decline of somatic and neural integrity. While the global burden of dementia continues to rise, scalable markers that capture this systemic vulnerability to identify individuals at risk remain scarce. Phase angle (PhA), a bioelectrical impedance analysis-derived metric reflecting cellular membrane integrity and body cell mass, has been linked to frailty and mortality; however, its potential as a sentinel for cognitive decline has not been systematically...

RAS family proteins, including HRAS, NRAS, and KRAS, are frequently mutated in cancer. Although there has been recent success in designing inhibitors that target oncogenic RAS, they elicit resistance and treating RAS-driven cancer remains difficult. Here, employing a proteomic analysis, we find that multiple spliceosome components are upregulated in the nuclei of cells undergoing RAS-induced senescence. This upregulation depends on RAS signalling and occurs in both senescent preneoplastic and...

Pancreatic islets maintain glucose homeostasis through coordinated action of endocrine and affiliate cell types and are central to type 2 diabetes (T2D) genetics and pathophysiology. Our understanding of robust human islet cell type-specific alterations in T2D remains limited. Here, we report comprehensive single-cell transcriptome profiling of 245,878 human islet cells from 48 donors spanning non-diabetic, pre-diabetic, and T2D states, and we identify 14 distinct cell types detected in every...

Whole-genome duplication (WGD) of diploid cells triggers various cell fates, such as cell death, cell cycle arrest, and proliferation with chromosome instability, contributing to broad bioprocesses, including differentiation, tumorigenesis, or aging. However, factors determining the post-WGD cell fates remain largely unknown. In this study, we found that cytokinesis failure (CF) and mitotic slippage (MS), two major routes of WGD induction, differentially affected post-WGD viability and...

The naked mole-rat (NMR) is a subterranean rodent known for its unique thermal biology, exceptional longevity, and resistance to cancer and hypoxia. However, its thermal biology remains controversial, with various reports describing NMRs as poikilotherms, heterotherms, mesotherms, or partial homeotherms. Here, we investigated whether the thermogenic potential of NMR brown adipose tissue and its UCP1 differ from those in mice and whether the lack of thermal insulation causes extreme changes in...

Monitoring molecular activities within single live cells is vital for understanding cellular differentiation, senescence, heterogeneity, and disease progression. However, conventional single-cell analyses often rely on micromanipulation or extraction followed by downstream measurements, which cannot capture in situ real-time dynamics. Fluorescent labeling and electrochemical methods provide temporal resolution but face limitations in labeling, substrate scope, and multiplexing. Here, we present...

Somatostatin/allatostatin C signaling regulates sleep, metabolism, memory, and longevity, but the underlying neuronal mechanisms remain unclear. We investigated the Caenorhabditis elegans somatostatin/allatostatin C ortholog NLP-99 and its receptor NPR-16. We found that the wake-active AIY neurons release NLP-99 to activate NPR-16. NPR-16 is G(i/o) coupled and acts cell nonautonomously to activate the sleep-active RIS neuron while acting autonomously in RIS to inhibit calcium activation and the...

To determine the genes and pathways that are up- or down-regulated in a consistent manner throughout the rodent lifespan, we generated a high N age-related gene expression atlas in mice and rats, by profiling 28 tissues in male and female C57BL/6J mice and 32 tissues in male Sprague Dawley rats (>5000 samples) over multiple time points. We identified age-related genes and pathways that change either early in life, at mid-age, late in life, or linearly throughout the animals' lifespan. Linear...

Depletion of TRF2 from chromosome ends causes telomeric fusions and genome instability in mammals, but in mouse neural stem cells (mNSCs), Trf2's role is non-telomeric. Although essential for mNSC proliferation and survival, Trf2 does not protect telomeres, aligning with findings that Trf2 is dispensable for telomere protection in pluripotent stem cells. In Trf2-deficient adult mNSCs (Trf2fl/fl; Nestin-Cre), proliferation decreased and neuronal differentiation was impaired, yet no telomere...

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Understanding how aging reshapes balance is essential for targeted assessment and rehabilitation. Because wobble boards impose continuous instability, their kinematics may provide a noninvasive readout of long-latency (transcortical) reflex function in ecologically valid conditions. We analyzed wobble-board dynamics in healthy younger adults ( 19 -- 35 y, n = 29 ) and community-dwelling older adults ( 56 -- 70 y, n = 29 ) performing with and without a concurrent cognitive load (Trail...

Cortical thinning and atrophy are hallmarks of brain aging that have been characterized using magnetic resonance imaging (MRI). Brain aging involves many neuroanatomic features whose effects on brain structure remain unexplored. To address this challenge, we trained interpretable deep neural networks (DNNs) to estimate brain age (BA) from T(1)-weighted (T(1)w) MRI. By identifying MRI features unapparent to humans, DNNs can find aging-related structural alterations above and beyond cortical...

CONCLUSION: Integrating assessments for multisensory impairment, vision, and hearing loss may add to elder mistreatment prevention and detection efforts.

Alzheimer's disease (AD) is an aging-associated neurodegenerative disorder characterized by amyloid-β (Aβ) and tau accumulation and progressive cognitive decline. Increasing evidence implicates the glymphatic system, a brain-wide perivascular pathway involved in cerebrospinal fluid-interstitial fluid exchange and metabolic waste clearance, in the removal of Aβ, tau, and other solutes relevant to AD pathogenesis. Aging-related alterations in aquaporin-4 polarization, arterial pulsatility, sleep...

CONCLUSION: The selection of QSM reconstruction pipelines impacts results obtained from multi-site studies, indicating the importance of harmonizing QSM pipelines when interpreting susceptibility measures across studies.

Cognitive flexibility is an executive function that enables adapting behaviour to a changing environment and is thus critical for daily life. The degree of its preservation upon healthy aging and the neural mechanisms underlying it are still a matter of debate. To investigate the electrophysiological correlates of cognitive flexibility in older age, we measured cognitive flexibility in 99 young (24.75 ± 4.45 years) and 83 older adults (69.19 ± 6.25) using electroencephalography (EEG). Compared...

Mutations in DNA damage repair (DDR) genes lead to genomic instability, driving a range of degenerative syndromes. In addition to promoting mutation accumulation, unrepaired DNA damage can leak into the cytosol and activate innate immune-sensing pathways, particularly the cGAS-STING axis. However, the extent to which cGAS causally contributes to organismal pathology in DDR syndromes in vivo remains unresolved. Here, we genetically model ataxia telangiectasia (A-T) and Bloom syndrome in the...

Transmembrane protein 65 (TMEM65) depletion in a patient caused severe mitochondrial encephalomyopathy, highlighting its clinical importance. Recent studies show TMEM65 acts as a mitochondrial Na^(+)/Ca^(2+) exchanger in vitro. Here, we generated conditional Tmem65 knockout mice to define its role in neuromuscular tissues in vivo. Both whole-body and nervous system-specific Tmem65 knockouts exhibited severe growth retardation and seizure-associated sudden death at ~3 weeks, establishing TMEM65...

Although seawater electrolysis holds great promise for green hydrogen production, the persistent challenges of chloride ions (Cl^(-))-induced chemical corrosion and localized acid etching under high potential severely hinder the lifespan of the anode. Herein, we propose that Os nanoparticles anchored on CoP nanowires supported by Ni foam (Os-CoP/NF) acts as a dual-protection anode with proton-buffering and Cl^(-)-repelling capabilities to simultaneously inhibit corrosion during seawater...

Aging is an important risk factor for Parkinson's disease (PD). Characterizing age-related alterations in the nigrostriatal system may help identify early vulnerability prior to overt neurodegeneration. We aimed to delineate aging trajectories of structure and hemodynamics of the nigrostriatal system and examine their associations with motor and cognitive functions. We analyzed 486 healthy adults from Human Connectome Project-Aging dataset, stratified into younger (≤ 60 years) and older (> 60...