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A Circadian Trough in Glucocorticoid Signaling Is Essential for Bone Health in Mice

2 hours 46 minutes ago
We previously demonstrated that flattening circadian glucocorticoid (GC) rhythmicity without increasing overall GC exposure induces an osteoporotic phenotype in mice. Here, we aimed to further elucidate the importance of the amplitude and timing of circadian GC oscillations for bone health. C57Bl/6J mice were implanted with vehicle or corticosterone slow-releasing pellets to flatten the circadian GC rhythm. To differentiate between the importance of circadian GC peaks or troughs, mice with...
Annelies E Smit

Neural and motor mechanisms of handwriting: from healthy aging to neurodegenerative disorders

2 hours 46 minutes ago
Handwriting is a complex cognitive and motor skill supported by a distributed brain network involving cortical, subcortical, and cerebellar regions responsible for planning, execution, and sensorimotor integration. Beyond its communicative role, handwriting provides biologically meaningful information about brain function and motor control, serving as a sensitive marker of both normal and pathological changes. Age-related alterations, such as reduced fine motor precision, impaired sensory...
Francesca Burgio

Brimonidine Therapy for Protection From Noise-Induced Hearing Loss

2 hours 46 minutes ago
Noise exposure is a known cause of hearing loss, and only a few effective preventive drugs are available. Therefore, in this study, we aimed to investigate the protective effects of brimonidine on noise-induced inner ear hearing impairment in mice and explore its underlying mechanisms and long-term outcomes. Mice were randomly divided into control, noise exposure, and brimonidine groups. A 62-week follow-up was conducted after noise exposure. Brimonidine inhibited the noise-induced increase in...
Jing Cai

Vitamin C slows primate aging by targeting iron-driven lipid peroxidation

1 day 2 hours ago
Aging has long been associated with oxidative stress, yet its underlying metabolic drivers remain unclear. Liu et al. identify a conserved, iron-driven lipid peroxidation of primate aging mediated by ACSL4 and demonstrate that vitamin C directly suppresses this process, offering a translatable strategy to mitigate age-associated functional decline.
Pei-Long Yu

Polyunsaturated lipids kill senescent cells by ferroptosis

1 day 2 hours ago
In a recent Cell Press Blue paper, Zhang et al. identify two polyunsaturated lipids that selectively eliminate senescent cells by inducing ferroptosis, uncovering this iron-dependent cell death pathway as a vulnerability for senescent cells. Their findings position ferroptosis induction as a promising strategy for targeting senescence and aging-associated diseases.
Mariantonietta D'Ambrosio

Cell loss disrupts mechanical homeostasis to drive retinal pigment epithelium ageing-like phenotype in vitro

1 day 2 hours ago
Tissue homeostasis emerges from mechanical feedback loops balanced by cell loss and proliferation, a balance that in postmitotic tissues must be maintained without compensatory proliferation. Yet how these tissues preserve mechanical homeostasis and how this challenges function in ageing remains unclear. To establish the relationship between cell density, mechanical homeostasis, and function, we induced age-mimicking cell loss in a postmitotic retinal pigment epithelium (RPE) in vitro. This...
Teodora Piskova

Cytokine multimerization: when more is more and sometimes less

1 day 2 hours ago
Cytokines are essential mediators of immune functions and regulate many other biological processes, ranging from fetal development to ageing. Dysregulation of cytokine responses can substantially increase the risk of disease and so their activity requires tight control. The formation of cytokine homodimers, heterodimers and multimers has evolved as a versatile mechanism to regulate cytokine biology, in which multimerization can enable or attenuate their activity, diversify signalling outcomes...
Ina Rudloff

Impact of miR-181a-5p and miR-1249-3p treatment on the visceral adipose tissue transcriptome of female mice

1 day 2 hours ago
MicroRNAs (miRNAs) regulate gene expression and can influence processes such as inflammation, metabolism, and aging. This study assessed the effects of miR-181a-5p and miR-1249-3p mimics on the transcriptome of visceral adipose tissue in middle-aged females mice. Mice received intraperitoneal injections of either miR-181a-5p, miR-1249-3p, or vehicle control, followed by transcriptomic and metabolic analyses. Both treatments significantly reduced fasting blood glucose levels and promoted...
Driele N Garcia

Oocyte aging in focus: Environmental and endogenous stressors driving reproductive potential decline

1 day 2 hours ago
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...
Katarzyna Ratajewska

Physical Fitness Is Negatively Associated With DNA Methylation-Based Risk of Aging-Related Diseases

1 day 2 hours ago
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...
Samiha Nasser

Senolytic Treatment Reduces Acute and Chronic Lung Inflammation in an Aged Mouse Model of Influenza

1 day 2 hours ago
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...
Lou Delval

Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity

1 day 2 hours ago
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...
Lucas P Scheidemantel

A human iPSC model of tauopathies engineered for 4R tau isoform expression endogenously develops late-stage neuronal tau pathology

1 day 2 hours ago
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...
Angelika Dannert

Integration of aged brain multi-omics reveals cross-system mechanisms underlying Alzheimer's disease heterogeneity

1 day 2 hours ago
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...
Lucas P Scheidemantel

China's demographic dividend has moved from age-based labor supply to skill-based productivity

1 day 2 hours ago
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,...
Hengyu Gu

Age-stratified genomic analyses reveal population-specific genetic determinants of exceptional longevity in Taiwan

1 day 2 hours ago
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...
Ming-Shun Hsieh