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CONCLUSION: The findings elucidate a complex interplay between cardiovascular health and auditory function, emphasizing that heart attacks may exacerbate HL through the frailty pathway in certain older populations. These results highlight the need for tailored cardiovascular interventions and proactive measures to mitigate HL risks. Future research should focus on defining these pathophysiological associations more clearly to develop targeted interventions for vulnerable older people.

CONCLUSION: Our findings highlight that maintaining physical activity, particularly during middle adulthood, is associated with reduced risk of sarcopenia. Because physical activity was self-reported, future research should employ objective measures and longitudinal designs to confirm these associations.

Type 2 diabetes (T2D) impacts the quality of life and lifespan of nearly 10% of the global population. Human islet amyloid polypeptide (hIAPP) constitutes a major component of islet amyloid deposition in patients with T2D, with hIAPP fibrils believed to play a key role in the pathogenesis of T2D. In this study, we determined the cryo-electron microscopy (cryo-EM) structure of hIAPP fibrils extracted from surgically resected pancreases of three donors with T2D. These fibrils exhibit a uniform...

We report the discovery of a chemical series that enhances ApoE secretion from human astrocytes through mechanisms independent of LXR agonism. Target deconvolution of hits from a phenotypic screen in astrocytoma cells employed chemoproteomics, photoaffinity probes, in vitro KINOMEscan analysis, and targeted siRNA knockdown experiments. Photoaffinity labeling coupled with quantitative chemical proteomics identified aryl hydrocarbon receptor (AhR), a transcription factor not previously associated...

The mechanisms for failure of neoadjuvant immune checkpoint blockade (NICB), an established therapy for patients with esophageal squamous cell carcinoma (ESCC), remain unclear. We integrated single-cell RNA data from patients with ESCC pre- and post-NICB, identifying a subset of senescent EGR1-expressing B cells that correlate with poor pathological responses. EGR1 was a key transcription factor regulating B cell senescence. EGR1^(+) B cells emerged as predictors of adverse outcomes in multiple...

Rapid urbanization has driven widespread increases in artificial light at night, intensifying energy use, light pollution, and sustainability challenges. However, its ecological impacts, particularly on vegetation phenological transitions, remain poorly understood. Using 62,994 site-year in situ records and satellite observations across 452 cities from 2001 to 2022, we show that elevated levels of artificial light at night are associated with delayed dates of foliar senescence in urban areas....

Genotoxic drugs used to treat cancer can trigger senescence, which contributes to chemotherapy resistance and tumor heterogeneity. However, the resulting cellular and molecular alterations following senescence remain poorly characterized. In this study, chemotherapy-induced senescence was triggered by etoposide in MDA-MB-231 breast cancer cells, and their fibrogenic potential, epithelial-to-mesenchymal transition (EMT), and stemness features were examined. In these cells, key mediators of...

Exposure to fine particulate matter (PM2.5) triggers pulmonary inflammation and oxidative stress, which can lead to cellular senescence and a decline in lung function. Curcumin, a yellow polyphenol derived from the rhizome of Curcuma longa, is traditionally used to treat respiratory ailments. However, its potential to counteract PM2.5-induced pulmonary senescence remains underexplored. In this study, we established a murine model of PM2.5-triggered lung senescence and used BEAS-2B cells to...

Type 2 diabetes (T2D) impacts the quality of life and lifespan of nearly 10% of the global population. Human islet amyloid polypeptide (hIAPP) constitutes a major component of islet amyloid deposition in patients with T2D, with hIAPP fibrils believed to play a key role in the pathogenesis of T2D. In this study, we determined the cryo-electron microscopy (cryo-EM) structure of hIAPP fibrils extracted from surgically resected pancreases of three donors with T2D. These fibrils exhibit a uniform...

No abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population. Although frailty has been recognized as a potential risk factor, previous studies relying on static assessments cannot capture its dynamic nature. This study aims to prospectively evaluate the association between dynamic frailty trajectories and incident AMD. The baseline cohort included 462,573 UK Biobank participants who were free of AMD and had frailty phenotype (FP) data at...

Glucagon, a key hormone in maintaining euglycemia during fasting, also exerts broad metabolic effects, including regulation of lipid oxidation, adiposity, insulin sensitivity, and metabolic rate. However, its role in aging and longevity remains largely unexplored, a significant omission given the extensive research on dietary restriction and insulin signaling in lifespan modulation. Here, we investigated the impact of hepatic glucagon receptor (GCGR) signaling on lifespan using a liver-specific...

Aging is a heterogeneous process, with organ systems and individuals experiencing variable rates of decline that are not fully reflected by chronological age. This variability contributes to the complexity of system morbidity, which poses increasing challenges for clinical care and biomedical research. In this review, we discuss the heterogeneity of organ and whole-body aging and perspectives on genomics as possible mechanisms that relate to such heterogeneity. We discuss how static genomics,...

Cell states and biological processes are defined by their epigenetic profiles, distinctive composites of DNA- and histone-based chromatin components. However, the specific histone posttranslational modifications that distinguish cellular senescence and the impact of their distribution on transcription, especially with regard to gene length, have not been fully elucidated. Here, we show that promoter loss of symmetric dimethylated H4R3 (H4R3me^((2s))) and spreading of trimethylated H3K79...

Age-varying DNA methylation sites reflect increasing interindividual epigenetic divergence during aging, offering insights into health heterogeneity and potential for personalized interventions. Leveraging longitudinal DNA methylation data (3 waves over 5 years) from 135 relatively healthy Chinese older adults in the Rugao Longitudinal Ageing Study, we systematically characterized dynamic DNA methylation changes with age via mixed-effects modeling, identifying 125,353 age-associated (i.e., sites...

Testicular aging, a key feature of late-onset hypogonadism (LOH), is closely associated with Sertoli cells dysfunction. Emerging evidence implicates lipid droplet (LD) accumulation as a hallmark of aging in Sertoli cells, but its role in Sertoli cells senescence and the associated molecular mechanisms are unknown. We found that aging and obesity drove progressive LD accumulation in Sertoli cells, accompanied by mitochondrial dysfunction and ROS overproduction. Palmitic Acid (PA)-induced LD...

Parkinson's disease (PD) is characterized by dopaminergic neuron loss, motor dysfunction, and Lewy body formation. Src homology 2B adaptor protein 2 (SH2B2), a member of the SH2B family with known roles in neuroregulation, has not been fully explored in PD. This study aimed to investigate the neuroprotective effects and mechanisms of SH2B2 in PD. MPTP-induced mouse model and MPP^(+)-treated SH-SY5Y cell model were established to simulate PD in vivo and in vitro. Mice were randomly divided into...

CONCLUSIONS: IC, particularly in the domains of cognition and mobility, was prevalently impaired among older adults. We identified both common and domain-specific factors associated with IC, offering insights for developing targeted interventions to enhance IC.