Aging & Longevity

Homologous recombination (HR) is traditionally portrayed as a DNA double-strand break repair pathway. However, emerging evidence positions RAD51, its partners BRCA1, BRCA2, and other HR factors at the core of a broader genome-maintenance network that operates by a "prevent and protect" strategy extending beyond repair. Here, we review how RAD51 can shield DNA from nucleolytic processing mediated by MRE11 and related nucleases, promote fork reversal, suppress replicative DNA gaps accumulation,...

CONCLUSION: The ACP training program has successfully engaged staff in care homes by increasing their capacity, opportunity, and motivation.

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.

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...

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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...

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.

The human gut microbiome (GM) is increasingly recognized as one of the main systems influencing the aging trajectory. Age-related dysbiosis, with imbalance between symbionts and pathobionts, can in fact fuel chronic inflammation (inflammaging) and promote frailty. In older individuals, GM composition is characterized by marked inter-individual variability and consistently influenced by environmental exposures. Studies conducted in animals and closed human communities suggest that social contacts...

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Hematopoietic stem cells (HSCs) reside in the bone marrow in a quiescent state, but can be mobilized into the blood in response to inflammation, cytokine stimulation, nervous activity or hypoxia. Chronic inflammation, a hallmark of aging, accelerates HSC aging by promoting myeloid-biased differentiation and reducing self-renewal capacity, yet the role of mechanical stimulation in regulating these processes remains poorly understood. Here, we found that PIEZO1 senses shear stress in blood flow to...