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Evaluation of statistical differential analysis methods for identification of senescent cells using single-cell transcriptomics
Differential gene expression (DGE) analysis is a crucial step in identifying senescent cells using single-cell RNA sequencing (scRNA-seq) data. However, few studies have evaluated the performance of DGE methods-particularly those implemented in the widely used Seurat package. In this study, we systematically assessed 10 DGE methods available in Seurat-Wilcox, Wilcox-limma, bimod, roc, t, negbinom, Poisson, LR, MAST, and DESeq2-using simulated and real scRNA-seq datasets. We evaluated each...
exBAClock: A comprehensive database of published clocks for age quantification and age-related diseases
Biological age, as opposed to chronological age, quantifies the body's functional state and rate of aging. Despite the absence of a universal formula for its determination, panels of biomarkers that change consistently with age are used to construct predictive aging clocks. These models enable the identification of accelerated aging and are valuable as surrogate endpoints in clinical trials. The proliferation of published aging clocks has created a challenge: data is fragmented across numerous...
The effects of extracellular matrix degradation mediated by chronic inflammation in aged skin on the structure and function of eccrine sweat glands
Eccrine sweat glands (ESGs) are critical organs for human thermoregulation, yet their function progressively declines with aging. This study aims to investigate the underlying mechanisms responsible for the age-related impairment of ESG function. Through comparative analysis between skin tissues from young and aged mice/human, we observed structural loosening of aged ESG and a significant reduction in the expression of extracellular matrix (ECM) components-type I and type II collagen. Further...
Age and mating status modulate combined efficacy of α-lipoic acid and climbing to mitigate high-fat diet-induced oxidative stress in Drosophila melanogaster
High-fat diet (HFD) intake is a potent inducer of oxidative stress, promoting metabolic dysfunction and accelerated ageing. Identifying interventions capable of mitigating this persistent redox burden is therefore essential. This study investigated the combined efficacy of α-lipoic acid (LA) supplementation and a daily climbing regimen in counteracting HFD-induced oxidative stress across different life stages and mating statuses in Drosophila melanogaster. Flies were maintained on an HFD and...
A Scalable Organoid Model of Urothelial Aging for Metabolic Interrogation, Infection Modeling, and Reversal of Age-Associated Changes
Aging leads to a progressive decline in overall bladder function resulting in lower urinary tract symptoms and increased susceptibility to infections. However, tissue-specific mechanisms of aging, specifically the contributions of the urothelium, remain elusive. Here, we introduce mouse bladder epithelium-derived organoids (mBEDOs) as a scalable platform to model urothelial aging. mBEDOs from aged mice recapitulate key features of age-associated cellular reprogramming, including oxidative...
A roadmap for conducting more inclusive research on brain resilience in ageing and dementia
The variability in cognitive and brain ageing trajectories may be influenced by inter-individual and community-level differences in resilience that result from differential exposures to social and structural determinants of health and be affected by an individual's sex and gender. However, no clear guidance exists on how to best integrate these diversity-related factors (that is, sex, gender and social and structural determinants of health) into clinical and cognitive neuroscience research on...
Social frailty, functional ability and social capital: a study among urban slum older adults in Tamil Nadu, India-convergent parallel mixed method study
BACKGROUND: Social frailty and reduced functional ability are major challenges among older adults in urban slums, yet the mechanisms linking these factors remain poorly understood. Social capital may buffer the effects of social frailty, but evidence is limited in urban slums context. The protocol study hypothesized that higher social capital is associated with lower social frailty and better functional ability among older adults.
A monoclonal antibody targeting the C-terminal of alpha-synuclein fibrils mitigates pathology in a Parkinson's disease model
Parkinson's disease (PD) pathogenesis is driven by α-synuclein (α-syn) amyloid aggregation, with the flexible C-terminal region mediating pathological interactions with cellular receptors and facilitating disease propagation and neuroinflammation. Through immunization with human α-syn fibrils and iterative neuronal binding and propagation assays, we identify H21 as a high-affinity fibril-specific monoclonal antibody. H21 selectively binds to α-syn fibrils and specifically targets the C-terminal...
Cortical O<sub>2</sub> supply and metabolism are suppressed in the aged mice
Current evidence suggests that the rejuvenating effects of parabiosis on brain function arise from the exchange of blood factors that enhance synaptic plasticity, promote neurogenesis, and reduce neuroinflammation in aged animals. However, aging is also associated with diminished tissue oxygenation. Here, we report that erythrocytes (red blood cells, RBCs) from aged mice exhibit reduced responsiveness to low oxygen tension (PO(2)) and release O(2) slower than those from young mice. In vivo,...
MTFR1L is a cardiac antiaging factor for maintenance of mitochondrial homeostasis
Mitochondrial dysfunction is a hallmark of aging and a key contributor to age-related diseases including cardiovascular disease. However, molecular pathways that safeguard mitochondrial homeostasis in the aging heart remain poorly understood. Here, we identify MTFR1L as a regulator of mitophagy that binds p-S65-Ub, a key signal amplifying the PINK1/Parkin axis. We find that MTFR1L is enriched in metabolically active tissues, particularly in the heart, where it regulates Parkin signaling. Genetic...
Age-driven dysbiosis: gut microbiota in the pathogenesis and treatment of aging disorders
Aging, a complex physiological and molecular process, has undergone significant changes, of which gut microbiome composition has surfaced as an important key in the maintenance of neurological health. Recent studies have revealed the significant impact of age-related gut dysbiosis in the induction of neuroinflammation, metabolic syndrome, disruptions in gut-brain axis, and age-related neurological decline. Although significant studies have revealed the impact of the microbiome-gut-brain axis in...
Hierarchical disruption of lateral prefrontal cortex gradients in cognitive aging
The lateral prefrontal cortex (LPFC) plays a pivotal role in executive functions and exhibits a hierarchical rostro-caudal organization critical for higher-order cognition. Using connectome gradient mapping of resting-state fMRI data across young, middle-aged, and older adults (N = 478), we found preserved global gradient structure but significant compression of the principal gradient in older adults relative to middle-aged adults, particularly in dorsolateral (DLPFC) and frontopolar (FPC)...
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