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Oocyte aging in focus: Environmental and endogenous stressors driving reproductive potential decline
Oocyte quality, a critical determinant of female reproductive potential, experiences a progressive decline with age, largely driven by the cumulative effects of oxidative stress and mitochondrial dysfunction. This review thoroughly synthesizes the latest evidence concerning the molecular, cellular, and environmental factors that disrupt redox homeostasis within oocytes. It particularly highlights the pivotal roles of reactive oxygen species, impaired mitochondrial metabolism, epigenetic...
Physical Fitness Is Negatively Associated With DNA Methylation-Based Risk of Aging-Related Diseases
Physical fitness is a key determinant of health, yet the molecular pathways linking fitness to the risk of aging-related diseases remain unclear. We examined associations between DNA methylation-based protein level estimates (EpiScores) and five fitness traits-VO(2)max, GripStrength, JumpMax, body mass index (BMI), and cognition-in a cohort of 290 mostly old individuals (mean age of 60 ± 11 years). EpiScores for 109 plasma proteins were obtained using the MethylDetectR tool and tested for...
Senolytic Treatment Reduces Acute and Chronic Lung Inflammation in an Aged Mouse Model of Influenza
Influenza A virus continues to pose a significant global health burden, with older individuals experiencing disproportionate morbidity and mortality. Although aging is associated with the accumulation of senescent cells, the extent to which cellular senescence contributes to influenza severity remains poorly understood. The aim of this study was to evaluate the therapeutic potential of the senolytic drug ABT-263, a B cell lymphoma-2 inhibitor, in mitigating both acute and chronic damage in an...
Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity
The molecular correlates of Alzheimer's disease (AD) are increasingly being defined by multi-omics. However, findings from different data types are often difficult to reconcile. Here, we apply a data-driven multi-omics framework integrating seven omics layers from up to 1,358 aged human brain samples from the Religious Orders Study and Rush Memory and Aging Project. We demonstrate sprawling cross-omics biological factors relating to AD phenotypes. The strongest AD-associated factor (factor 8) is...
A human iPSC model of tauopathies engineered for 4R tau isoform expression endogenously develops late-stage neuronal tau pathology
Tauopathies, such as Alzheimer's disease and frontotemporal dementia, are common neurodegenerative diseases characterized by misfolding, hyperphosphorylation, and aggregation of tau. Molecular mechanisms underlying tauopathies are still poorly understood, which is in part due to a lack of human models autonomously developing major disease hallmarks. The formation of late-stage disease phenotypes may require adult tau isoform expression, which contributes to tau pathogenesis but is challenging to...
Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity
The molecular correlates of Alzheimer's disease (AD) are increasingly being defined by multi-omics. However, findings from different data types are often difficult to reconcile. Here, we apply a data-driven multi-omics framework integrating seven omics layers from up to 1,358 aged human brain samples from the Religious Orders Study and Rush Memory and Aging Project. We demonstrate sprawling cross-omics biological factors relating to AD phenotypes. The strongest AD-associated factor (factor 8) is...
China's demographic dividend has moved from age-based labor supply to skill-based productivity
Accelerated global population aging challenges conventional economic growth paths. Yet, the mechanisms underlying the transition from the age-based demographic dividend, derived from a favorable age support ratio (ASR), to a skill-based dividend, driven by human capital accumulation, remain insufficiently understood. Using population census data for 336 Chinese cities from 2000 to 2020, we develop a task-based skill ratio (TSR) index to quantify the skill composition of local labor markets,...
Age-stratified genomic analyses reveal population-specific genetic determinants of exceptional longevity in Taiwan
Human longevity arises from complex genetic and environmental interactions, yet the genetic basis of survival to extreme old age remains underexplored in Asian populations. We performed genome-wide association studies (GWAS) in a Taiwanese cohort, defining survival thresholds at ≥ 85, ≥ 90, and ≥ 95 years, and validated significant loci in an independent cohort. Multiple loci, including ZNF806, NUAK1, TANC1, SLC22A3, PTPRD, and PCSK2, were associated with longevity, of which 14 replicated with...
The Bright Side of Life: Optimism and Risk of Dementia
CONCLUSION: Higher optimism was associated with a lower incidence of dementia. These findings suggest a potential value of optimism in supporting healthy aging, which could be considered in future research on dementia prevention initiatives.
Systemic proteomic and organ aging signatures associated with plasma Abeta oligomerization in a Korean cohort: a cross-sectional study
CONCLUSION: Our findings demonstrated OAβT as a reflection of systemic changes linked to early AD pathology. Moreover, the influence of medications and systemic aging on OAβT values pointed to the potential avenues for intervention and emphasized the importance of considering systemic factors in AD pathogenesis and treatment.