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Role of LIMK1-cofilin-actin axis in dendritic spine dynamics in Alzheimer's disease

3 months 2 weeks ago
Dysregulation of dendritic spine dynamics, a process essential for synaptic plasticity and memory, is a hallmark of Alzheimer's disease (AD). Actin dynamics, largely regulated by the LIMK1-cofilin pathway, are central to maintaining structural and functional stability in neurons. In healthy brains, the LIMK1-cofilin-actin axis modulates actin polymerization within dendritic spines, supporting spine growth and plasticity. However, in AD, this pathway is altered, leading to both actin and synaptic...
Fabiola Paciello

Three dimensional multiscalar neurovascular nephron connectivity map of the human kidney across the lifespan

3 months 2 weeks ago
The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation...
Liam McLaughlin

Epigenetic regulation of neural stem cell aging in the mouse hippocampus by Setd8 downregulation

3 months 2 weeks ago
Neural stem cells (NSCs) in the mammalian brain decline rapidly with age, leading to impairment of hippocampal memory function in later life. However, the relationship between epigenetic remodeling and transcriptional regulation that compromises hippocampal NSC activity during the early stage of chronological aging remains unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on NSCs and newly generated neurons across different stages....
Shuzo Matsubara

Cysteine depletion triggers adipose tissue thermogenesis and weight loss

3 months 2 weeks ago
Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces 'browning' of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue. Systemic cysteine depletion in mice causes...
Aileen H Lee

ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging

3 months 2 weeks ago
Reactive thiols of proteinaceous cysteines are vital to cell biology by serving as sensor, effector and buffer of environmental redox fluctuations. Being the major source, as well as the prime target, of reactive oxygen species (ROS), mitochondria confront great challenges in preserving their thiol pool. Here we show that ROS modulator 1 (ROMO1), a small inner mitochondrial membrane protein, plays a role in protecting the mitochondrial cysteinome. ROMO1 is redox sensitive and reactive and...
Fengli Xu

The secretome of senescent monocytes predicts age-related clinical outcomes in humans

3 months 2 weeks ago
Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence and related them to clinical traits in humans to facilitate future noninvasive assessment of individual senescence burden, and efficacy testing of novel senotherapeutics. Using a nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in THP-1 monocytes and examined these proteins in 1,060 plasma samples...
Bradley Olinger

Morphological features of the domestic house cricket (Acheta domesticus) for translational aging studies

3 months 2 weeks ago
Aging alters morphology and locomotor function in diverse organisms, yet standardized model systems for studying these changes remain limited to a relatively few species. Here, we present a comprehensive analysis of age- and sex-dependent morphological variations in house crickets (Acheta domesticus), integrating refined husbandry protocols to enhance reproducibility and translational relevance. To ensure data consistency, we implemented a standardized husbandry framework incorporating...
Gerald Yu Liao

Nicotinamide Riboside Supplementation Benefits in Patients With Werner Syndrome: A Double-Blind Randomized Crossover Placebo-Controlled Trial

3 months 2 weeks ago
Werner syndrome (WS) is a rare hereditary progeroid syndrome caused by mutations in the WRN gene. Patients frequently develop various age-associated diseases prematurely, often leading to early mortality (≤ 60 years of age). Depletion of nicotinamide adenine dinucleotide (NAD)^(+) has been reported in patients with WS, suggesting a key role in the pathogenesis of WS. NAD^(+) supplementation may improve the condition of WS and other accelerated aging diseases. Therefore, we conducted a...
Mayumi Shoji

Cocota's Story: Life Lessons in Aging, Resilience, and End-of-Life Agency From a Brazilian Matriarch

3 months 2 weeks ago
Resilience is increasingly recognized as a central factor in how older adults adapt to life's inevitable changes, yet many clinicians remain unfamiliar with its practical applications in late life. Drawing on the true story of Cocota, a Brazilian matriarch who lived to be 100, this special article illustrates how resilience is neither a static trait nor limited to mere survival. Instead, it emerges over decades, shaped by early adversities and sustained through purposeful roles, strong social...
Thiago J Avelino-Silva

The prevalence of functional limitations in the US workforce

3 months 2 weeks ago
This research paper investigates the prevalence of functional limitations among employed adults in the United States and the association between these limitations and medical conditions. The authors administered a survey adapted from the Dutch Functional Abilities List to a nationally representative sample of US adults ages 22 and older, finding that nearly three-quarters of working adults report at least one functional limitation, with an average of nearly six functional limitations per working...
Hailey Clark