Aging & Longevity

We previously established distinct roles for the transcriptional elongation factors PAF1, negative elongation factor (NELF), SPT4/5, and SPT6 using auxin-inducible degron systems in human cell lines. Here, we integrate long- and short-read RNA-seq data from these degron lines to quantify transcript isoform usage at single-molecule resolution, identifying elongation factor-specific RNA processing regulons, including a cellular senescence-enriched regulon impacted by NELF and SPT6. Long-term NELF...

Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators driving cancer development and potential therapeutic targets across multiple human malignancies. However, their mechanistic roles during head and neck squamous cell carcinoma (HNSCC) initiation and progression remain incompletely elucidated. Here, we identified a novel oncogenic lncRNA, LINC00973, which was aberrantly upregulated in clinical samples and associated with aggressive clinicopathological features and adverse clinical...

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), which is associated with changes in microglia function. While age remains the biggest risk factor, the underlying molecular cause of PD onset and its concurrent neuroinflammation are not well understood. Many identified PD risk genes have been directly linked to dopamine neuron impairment, while others are linked to immune cell function. In this study, we found that the PD...

Aging clocks use machine learning to estimate biological age as a proxy for general health state. Here, we critically examine their practical value, highlighting fundamental challenges: abstract definitions, inconsistent clinical validation, and ignored prediction uncertainty. By comparing aging clocks with expert risk scores, direct outcome predictors, and emerging large health models, we question their benefits and encourage researchers to explicitly justify clock advantage over established...

Black rice diets are enriched with unsaturated fatty acids that are thought to be beneficial for neurodegenerative disorders in aging. Here we find that α-linolenic acid (ALA) and 11,14-eicosadienoic acid (EDA), which are naturally enriched in black rice, inhibit amyloid pathology, rescue cognition and extend lifespan in mouse preclinical models of Alzheimer's disease via allosteric activation of G protein-coupled receptor 120 (GPR120) in plaque-associated macrophages and activated microglia. We...

Normal aging triggers substantial topological transformation within resting-state electroencephalography (rs-EEG) networks. Given that the small-world (SW) architecture of hemispheric EEG networks may reflect an evolutionarily and developmentally optimized organization, investigating their modulations with age offers critical insights into the dynamic reorganization of functional connectivity (FC) patterns throughout adulthood. Utilizing rs-EEG data from a single-site public repository collected...

CONCLUSIONS: This large-scale study reveals a substantial burden of dementia in the studied Iranian provinces. The identified risk factors, including female sex, advanced age, widowhood, and low education, highlight vulnerable subgroups and underscore the urgent need for targeted public health strategies focused on early detection, risk reduction, and support systems for the elderly in Iran.

Centrifugation of biological matter in density gradient solutions is a standard method for separating cell types or components. It is also used to separate red blood cells (RBCs) by age, as they lose water and become denser over their lifespan. When the density gradient is prepared with Percoll, discrete bands of RBCs are systematically observed along the gradient, despite the continuous density distribution of RBCs. Early studies suggested that cell aggregation might influence spatial...

Aging disrupts intestinal stem cell (ISC) lineage fidelity, impairing epithelial barrier function and then promoting systemic health decline. In this study, we identify peroxisomal dysfunction as a critical driver of age-associated ISC mis-differentiation. Using Drosophila and mouse colonic organoids, we demonstrate that reduced PEX5 expression in aged ISCs impairs peroxisomal matrix protein import, leading to very long-chain fatty acids (VLCFAs) accumulation. In addition, we found that...

Topoisomerase III-beta (Top3b) reduces nucleic acid torsional stress and intertwining generated during RNA and DNA metabolism while protecting the genome from pathological R-loops, which otherwise result in DNA breakage and genome instability. By studying Top3b knockout mice (Top3b-KO), we find that the loss of Top3b accelerates the development of spontaneous atypical lymphoid hyperplasia and lymphomas arising in spleens and lymph nodes, organs with prominent Top3b expression. Aging Top3b-KO...

CONCLUSION: This study developed and internally validated a dynamic, nomogram-based scoring tool for early detection of MCI that integrates non-invasive retinal and visual biomarkers. The model demonstrated high discriminative power and substantial clinical net benefit. Further evaluation of the model's prognostic value in predicting further cognitive decline may support its clinical utility.

CONCLUSION: Postmenopausal women showed distinct epigenetic patterns in response to exercise, although these differences must be interpreted cautiously given the small premenopausal sample size. These results suggest potential immune cell-associated DNA methylation markers to inform personalized exercise strategies supporting healthy aging in women.

For memories to remain relevant and adaptive over the lifespan, modifications under specific conditions are required. Memory reconsolidation theory suggests that when a memory is reactivated, it can become labile, a state known as destabilization. This process is regulated by complex and dynamic neurobiological changes representing biological boundary conditions, which likely protect important memories from undergoing unnecessary or potentially maladaptive modifications. External cues, such as...

Diapause is an evolutionarily conserved strategy that enables many organisms to survive prolonged exposure to harsh environmental stressors. During this state, organisms drastically reduce their metabolic rate, halt development, and enhance stress tolerance in an energy-efficient manner. Remarkably, many diapausing organisms appear to substantially slow or suspend aging as a result of profound metabolic depression and developmental arrest. Consequently, diapause and aging appear to be programmed...

Sepsis-induced cardiac dysfunction is a major contributor to sepsis-related mortality, and many patients continue to experience long-term cardiac complications after recovery. Here, we demonstrate that cardiac senescence is a key feature of sepsis-associated cardiac dysfunction, with endothelial cells identified as the predominant senescent population in septic cardiac tissue. However, the pathogenic drivers of endothelial senescence in sepsis remain poorly characterized. Among potential...

Adult stem cells (SCs) transition between quiescent and active states to maintain tissue integrity, and dysregulation of this balance can lead to tissue degeneration, cancer, or premature aging. Both intrinsic factors and extrinsic niche signals influence these states; however, the molecular mechanisms that integrate extrinsic cues with intrinsic programs remain poorly understood. Here, we show that the conserved repressive histone mark, H2AK119ub, serves as a molecular switch linking inhibitory...

Biological clocks aim to estimate the physiological state of an organism, or of specific organs or systems, from the perspective of aging. The inferred individual age acceleration is presumably linked to increased mortality and morbidity risks. Here, we introduce a cognitive aging clock based on a battery of five tests (sensomotor arithmetic, sensomotor mirror letter, 1-back, campimetry and the Stroop), capturing sensory and verbal perception, working memory, and decision-making in the context...

Tree longevity is thought to increase in growth-limiting, adverse environments, but a quantitative assessment of drivers of global variation in tree longevity is lacking. We assemble a global database of maximum longevity for 739 tree species and analyse associations between longevity and climate, soil, and species' functional traits. Our results show two primary pathways towards long lifespans. The first is slow growth in resource-limited environments, consistent with the "adversity begets...

CONCLUSIONS: The Chinese version of BioPMovQ has good reliability and validity, and can be used to measure the relationship between pain and various factors related to exercise behavior in elderly patients with CMP from a biological behavioral perspective.

CONCLUSION: Among geriatric patients, a FRD appears to prevail, extending beyond a neutral acceptance of death's inevitability and existing independently of suicidality, depression, frailty, or disease burden. Understanding a FRD may help contextualize older individuals' acceptance of aging and could impact geriatric treatment outcomes.