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Parkinson's disease (PD) is a prevalent neurodegenerative disorder predominantly affecting individuals over 60. Its motor symptoms stem from the deterioration of dopaminergic neurons within the substantia nigra. Despite aging being a significant risk factor, the specific mechanisms linking aging and PD pathology remain unclear. Leveraging advancements in single-cell genomics, this study utilizes single-nucleus multiome sequencing to capture transcriptomic and epigenetic profiles from 40,125...

Population ageing has widened the gap between lifespan and healthspan, with frailty and functional dependence increasingly shaping late-life outcomes. Yet trajectories in older age remain highly heterogeneous, suggesting that vulnerability is not determined by chronological age alone but by differences in adaptive capacity. This review reframes resilience as a dynamic, multilevel construct linking molecular maintenance, regulation within the immune-endocrine-autonomic "vital systems triad," and...

Metastasis is the major cause of death for patients with triple-negative breast cancer and other solid malignancies. Metastases arise from cancer cells that disseminate from the original tumour, survive systemic immune surveillance and colonize new organs¹. Little is known about how initial disseminated tumour cells (DTCs) overcome anti-tumour immunity after seeding a new organ. Here we use a visible antigen in a model of triple-negative breast cancer with cognate CD8^(+) T cells to study the...

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The reduction in number and decreased differentiation capacity of oligodendrocyte progenitor cells (OPCs) directly affect myelination in demyelinating diseases and aging, but the underlying mechanisms remain incompletely characterized. Here we observed a marked decline in the number of OPCs during aging, notably within the subpopulation highly expressing Acss2, which encodes acetyl-CoA synthetase 2 (ACSS2). Deletion of ACSS2 in the oligodendrocyte lineage resulted in a reduced OPC population,...

To identify the pattern of cortical atrophy variation in Parkinson's disease (PD) and its contribution to clinical manifestations beyond dopaminergic dysfunction, 45 healthy controls (HCs) underwent MRI, and 222 participants with PD additionally underwent dopamine transporter (DAT)-PET, Unified PD Rating Scale (UPDRS), and neuropsychological tests. Using principal component analysis in PD, a single pattern in cortical thickness (PC1^(PD)) was identified. Linear regressions models were applied to...

Parkinson's disease (PD) is a prevalent neurodegenerative disorder predominantly affecting individuals over 60. Its motor symptoms stem from the deterioration of dopaminergic neurons within the substantia nigra. Despite aging being a significant risk factor, the specific mechanisms linking aging and PD pathology remain unclear. Leveraging advancements in single-cell genomics, this study utilizes single-nucleus multiome sequencing to capture transcriptomic and epigenetic profiles from 40,125...

Escitalopram is one of the most widely prescribed selective serotonin reuptake inhibitors (SSRIs) for treating depression and anxiety disorders in adolescents and pregnant women. While some SSRIs have been reported to extend lifespan, the impact of escitalopram on the aging process remains unclear. Here, we demonstrated that escitalopram administration at juvenile, young, or old adult stages significantly shortens lifespan and impairs healthspan in Caenorhabditis elegans. This pro-aging...

Individuals with hypoplastic left heart syndrome (HLHS) have an underdeveloped left ventricle and require surgery to reconfigure blood flow for survival. Here we profiled the HLHS right-ventricular microenvironment by single-nucleus RNA sequencing and spatial transcriptomics at birth (before heart failure), after surgery with heart failure and after ventricular assist device (VAD) unloading (reduced hypoxia and volume overload). We show that HLHS cardiomyocytes, both within the heart and when...

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Structural health monitoring (SHM) is vital for maintaining the safety and longevity of civil infrastructure, yet current solutions remain constrained by cost, power consumption, scalability, and the complexity of data processing. Here, we present a diffractive vibration monitoring system, integrating a jointly optimized diffractive layer with a shallow neural network-based backend to remotely extract three-dimensional (3D) structural vibration spectra, offering a low-power, cost-effective, and...

Radiotherapy is a key foundation of oncologic treatment that is used across the spectrum of cancer indications. Advances in imaging, treatment planning, and dose delivery have led to increasingly conformal and even ablative treatments, which have resulted in improved tumor control with no increase in the risk of side effects (or with a decrease in risk) as compared with previous treatments. These advances have facilitated the combined use of radiotherapy with efficacious systemic therapies,...

Vast study in Peru and Kenya confirms limited defenses against rising temperatures, redoubling climate concerns

Chaperone-mediated autophagy (CMA) is a selective autophagy pathway that targets specific proteins containing a KFERQ-like motif for lysosomal degradation. It has been shown by us and others that CMA decreases during physiological aging in most tissues, and its impairment is associated with increased incidence of age-related pathologies, such as cardiovascular disease, neurodegenerative disorders or sarcopenia. However, its involvement in age-related macular degeneration (AMD), a prevalent...

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Aging is accompanied by increasing inter-individual variability in cognitive and functional outcomes, reflecting differences in biological resilience and vulnerability. Chronic low-grade inflammation (inflammaging) is a central driver of this process, yet the contribution of individual inflammatory pathways to adaptive versus maladaptive brain aging remains incompletely understood. The NLRP3 inflammasome has been widely implicated in age-related neurodegeneration, but its physiological roles...

Deep neural networks (DNNs) trained on magnetic resonance images can estimate global brain age (GBA), which reflects women's neurological disease risk. GBA gap (GBAG), the difference between GBA and chronological age (CA), quantifies excessive global aging; local BAG (LBAG) has not been examined despite allowing voxelwise resolution. Using a novel DNN architecture, we estimate LBAG for 12,284 UK Biobank females with chronological ages (CAs) ranging between 46 and 82 years (y) and quantify how it...