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Heart-brain co-ageing: Phenotypic heterogeneity, molecular mechanisms and translational interventions

2 weeks 1 day ago
Population ageing has increased the burden of cardiovascular disease, cognitive decline and frailty in older adults. These conditions are often studied separately, yet increasing evidence suggests that the ageing heart, vasculature and brain are biologically interconnected. Using a hybrid design that combines a systematic literature search with narrative synthesis, this review summarizes current knowledge on heart-brain co-ageing, with emphasis on phenotypic heterogeneity, molecular mechanisms...
Haozhang Huang

Multikingdom Gut Microbiome and Immune Aging: A Host-Microbial Signaling Perspective

2 weeks 1 day ago
Immune aging comprises heterogeneous changes in hematopoietic output, immune-cell function, inflammatory regulation, and tissue-specific immune states. In parallel, the gut microbiome undergoes ecological and functional remodeling across the bacteriome, mycobiome, virome, and archaeome, but these changes do not define a single "aged microbiome" and vary with host health, frailty, diet, medication exposure, and environmental context. Here, we examine how multikingdom gut microbiome remodeling...
Bowen Jiang

Turning back the ageing clock? Brain age in neuroprotective and clinical interventions

2 weeks 1 day ago
Neuroimaging-derived brain age has emerged as an intuitive marker of brain health and cognitive longevity. The difference between brain age and chronological age, termed brain-predicted age difference (brain-PAD), quantifies deviation from normative brain ageing and may help evaluate whether interventions could attenuate brain ageing trajectories. This review synthesizes the methodological foundations of brain age estimation, factors linked to brain-PAD across healthy ageing and disease,...
Yuke Luo

Mitochondrial carbonic anhydrase-VB inhibition rescues brain endothelial stress and memory in Alzheimer's disease models

2 weeks 1 day ago
Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective cure, characterized by the cerebral parenchymal and vascular accumulation of aggregated amyloid-β (Aβ) and hyperphosphorylated tau. Cerebrovascular and mitochondria dysfunction are early causal events in the progression of AD. Previous studies support that inhibiting carbonic anhydrases (CAs) may prevent mitochondrial and cerebrovascular dysfunction in AD models. Here, we selectively target the mitochondrial...
Nicole L Lemon

Preclinical and first-in-human evaluation of VG-3927/SAR448851, an oral small-molecule TREM2 agonist for Alzheimer's disease

2 weeks 1 day ago
Microglial dysfunction is increasingly implicated in Alzheimer's disease (AD) pathogenesis, with loss-of-function variants in the microglial receptor TREM2 as major risk factors for late-onset AD. We report VG-3927, an oral, CNS-penetrant small-molecule TREM2 agonist that engages the transmembrane domains of TREM2 and its adaptor DAP12 to promote higher-order receptor complex formation and downstream signaling. VG-3927 and tool compound VG-3909 exhibited (sub)nanomolar potency, cooperated with...
Borislav Dejanovic

Hippo-YAP/TAZ signalling at the crossroads of brain ageing and neurological disorders: mechanisms, crosstalk, and therapeutic prospects

2 weeks 1 day ago
As life expectancy increases globally, ageing has emerged as the main risk factor driving the increasing burden of neurological disorders. Although advances have been made in understanding their pathogenesis, current therapies remain largely symptomatic and do not prevent disease progression. There is a growing body of evidence that these disorders share common molecular mechanisms, including oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy, ferroptosis, and...
Bhaskar Jyoti Dutta

Plasma biomarkers of neurodegeneration and physical performance in older adults

2 weeks 1 day ago
Physical performance declines with age, but its association with circulating neurodegeneration biomarkers remains unclear. Blood biomarkers including NT1, NfL, oAβ, and pTau217 may reflect early neurodegenerative changes linked to physical performance decline. Evidence linking these biomarkers to physical performance is limited. We analyzed older adults in the COSMOS Clinic substudy with baseline and two-year follow-up assessments of plasma NT1, NfL, and oAβ and a single assessment of pTau217....
Alice C von Alvensleben

Nanoconfinement-cooperated catalysis enables rapid tandem redox kinetics for wide-temperature lithium-sulfur batteries

2 weeks 1 day ago
The slow kinetics of sulfur cathodes caused by the high energy barriers of Li^(+) desolvation stem primarily from the structure of the inner Helmholtz plane (IHP). Herein, a synergistic strategy combining electrochemical tandem catalysis with spatial nanoconfinement is proposed to regulate the Li(solvent)(x)^(+) dynamics. As a proof-of-concept, the porous covalent organic framework (denoted as TPBD) decorated MXene is in situ constructed, acting as a tandem kinetic promoter. The theoretical...
Tianli Li

Radical-induced autoxidation dominates squalene oxidative aging under environmental conditions

2 weeks 1 day ago
Ozone has been viewed as the principal oxidant of skin oils and other unsaturated surface films, but their fate under realistic indoor conditions remains poorly constrained. Here, we use squalene (SQ), a major component of skin lipids, to investigate the dominant oxidation pathways in occupied indoor environments and laboratory flow reactors. With exposure to indoor air, SQ decay and reactive oxygen species (ROS) formation accelerated over time, consistent with autoxidation. Laboratory...
Xinke Wang

Metabolomic aging and mortality clocks based on ensemble learning identify systemic aging risk across the human life span in 18,476 individuals

2 weeks 1 day ago
Aging is characterized by progressive functional decline, yet metabolomic signatures across the human life span remain incompletely defined. Here, we profiled plasma metabolomes from 18,476 participants aged 1 to 96 years across six centers in China using nano-assisted laser desorption/ionization mass spectrometry (LDI-MS) and identified 56 representative age-associated metabolites. In a healthy cohort, we developed a stacking ensemble model to estimate metabolomic age and quantified metabolomic...
Linlin Cao

Multimodal neuroimaging and electrophysiological signatures in amnestic mild cognitive impairment with different amyloid-β deposition status: correlations with cognitive function and diagnostic value

2 weeks 1 day ago
CONCLUSION: The temporal scalp θ/α ratio and right precuneus gray matter volume are promising candidate non-invasive auxiliary biomarkers for Aβ pathological stratification in aMCI, rather than validated clinical diagnostic biomarkers. The multimodal model provides supplementary subtyping value within this single-center cohort, while external multicenter validation is mandatory before clinical application. This cross-sectional dataset cannot support prediction of longitudinal progression to AD...
Yang Liang

Age-related differences in behavioral and brain predictors of parkinsonism in autistic adults

2 weeks 1 day ago
Autistic adults experience lifelong motor differences and may have increased vulnerability to parkinsonism, yet behavioral and neuroanatomical correlates of motor challenges across adulthood remain poorly understood. We examined cross-sectional behavioral and motor-related brain region morphology in autistic (n = 123) and non-autistic (n = 102) adults aged 18-71 years using the Parkinsonism Screening Questionnaire (PSQ), Adult Repetitive Behavior Questionnaire-2 (RBQ-2A), finger tapping, and...
Manuela Velez Galindo

The Human Ovary Exhibits Dynamic Molecular Remodeling in the Decades Post-Menopause

2 weeks 1 day ago
The human ovary is among the first organs to show age-related functional decline, resulting in menopause. Beyond this transition, the postmenopausal ovary is often regarded as quiescent and remains poorly characterized. We analyzed the proteomes of healthy, non-pathological ovaries using mass spectrometry (data-independent acquisition) from 28 postmenopausal women (50-75 years old), stratified into three age groups (50-59, 60-69, ≥ 70). We quantified 5812 protein groups and observed progressive...
Mark A Watson