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Transformative advances in modeling brain aging and longevity: Success, challenges and future directions

8 months 1 week ago
Research on brain aging is crucial for understanding age-related neurodegenerative disorders and developing several therapeutic interventions. Numerous models ranging from two-dimensional (2D) cell-based, invertebrate, vertebrate, and sophisticated three-dimensional (3D) models have been used to understand the process of brain aging. Invertebrate models are ideal for researching conserved aging processes because of their simplicity, short lifespans, and genetic tractability. Moreover, vertebrate...
Varsha Pai

Transformative advances in modeling brain aging and longevity: Success, challenges and future directions

8 months 1 week ago
Research on brain aging is crucial for understanding age-related neurodegenerative disorders and developing several therapeutic interventions. Numerous models ranging from two-dimensional (2D) cell-based, invertebrate, vertebrate, and sophisticated three-dimensional (3D) models have been used to understand the process of brain aging. Invertebrate models are ideal for researching conserved aging processes because of their simplicity, short lifespans, and genetic tractability. Moreover, vertebrate...
Varsha Pai

Loss of the APP regulator RHBDL4 preserves memory in an Alzheimer's disease mouse model

8 months 1 week ago
Characteristic cerebral pathological changes of Alzheimer's disease (AD) such as glucose hypometabolism or the accumulation of cleavage products of the amyloid precursor protein (APP), known as Aβ peptides, lead to sustained endoplasmic reticulum (ER) stress and neurodegeneration. To preserve ER homeostasis, cells activate their unfolded protein response (UPR). The rhomboid-like-protease 4 (RHBDL4) is an enzyme that participates in the UPR by targeting proteins for proteasomal degradation. We...
Ylauna Christine Mégane Penalva

An Arabidopsis single-nucleus atlas decodes leaf senescence and nutrient allocation

8 months 1 week ago
With rapid advancements in single-cell RNA sequencing (scRNA-seq) technologies, exploration of the systemic coordination of critical physiological processes has entered a new era. Here, we generated a comprehensive Arabidopsis single-nucleus transcriptomic atlas using over 1 million nuclei from 20 tissues encompassing multiple developmental stages. Our analyses identified cell types that have not been characterized in previous single-protoplast studies and revealed cell-type conservation and...
Xing Guo

The role of heme in sepsis induced Kupffer cell PANoptosis and senescence

8 months 1 week ago
Elevated heme levels, a consequence of hemolysis, are strongly associated with increased susceptibility to bacterial infections and adverse sepsis outcomes, particularly in older populations. However, the underlying mechanisms remain poorly understood. Using a cecal ligation and puncture (CLP) model of sepsis, we demonstrate that elevated heme levels correlate with Kupffer cell loss, increased bacterial burden, and heightened mortality. Mechanistically, we identify mitochondrial damage as a key...
Tingting Li

Relationship between physical activity and DNA methylation-predicted epigenetic clocks

8 months 1 week ago
This study investigates the relationship between physical activity (PA) levels and DNA methylation (DNAm)-predicted epigenetic clocks in a U.S. population sample (n = 948, mean age 62, 49% female). Eight epigenetic clocks were analyzed, revealing that higher PA levels were significantly associated with younger biological ages across all indicators, with the strongest effects observed for SkinBloodAge and LinAge. Multivariable linear regression models, adjusted for sociodemographic and lifestyle...
Yanwei You

Disuse-driven plasticity in the human thalamus and putamen

8 months 1 week ago
Subcortical plasticity has mainly been studied using invasive electrophysiology in animals. Here, we leverage precision functional mapping (PFM) to study motor plasticity in the human subcortex during 2 weeks of upper-extremity immobilization with daily resting-state and motor task fMRI. We found previously that, in the cortex, limb disuse drastically impacts disused primary motor cortex functional connectivity (FC) and is associated with spontaneous fMRI pulses. It remains unknown whether...
Roselyne J Chauvin

Aged Gut Microbiota Contributes to Cognitive Impairment and Hippocampal Synapse Loss in Mice

8 months 1 week ago
Gut microbiota alteration during the aging process serves as a causative factor for aging-related cognitive decline, which is characterized by the early hallmark, hippocampal synaptic loss. However, the impact and mechanistic role of gut microbiota in hippocampal synapse loss during aging remains unclear. Here, we observed that the fecal microbiota of naturally aged mice successfully transferred cognitive impairment and hippocampal synapse loss to young recipients. Multi-omics analysis revealed...
Mingxiao Li

Oxidative stress at telomeres triggers internal DNA loops, TRF1 dissociation, and TRF2-dependent R-loops

8 months 1 week ago
Telomeres are the nucleoprotein structures at chromosome ends. Telomeres are particularly sensitive to oxidative stress, which can induce telomere damage, shortening, and premature cellular senescence. How oxidative damage influences telomere structure has not been defined. Here, we induce oxidative damage at telomeres using menadione, which damages mitochondria mimicking intrinsic oxidative stress. We find that oxidative stress induces at telomeres single-stranded DNA breaks, internal DNA loop...
Trang Thu Nguyen

Bryostatin-1 improves function in arteries with suppressed endothelial cell autophagy

8 months 1 week ago
We have previously reported that when autophagy is suppressed in endothelial cells (ECs), a glycolytic defect limits shear-stress -induced ATP production to an extent that purinergic 2Y1 receptor (P2Y1R)-mediated activation of EC nitric oxide (NO) synthase (eNOS) is compromised. Subsequently we demonstrated the functional relevance of this finding in arteries from mice with genetic, pharmacological, and age-associated EC autophagy impairment. Using gain and loss of function approaches in vitro,...
Jae Min Cho

HDAC11 deficiency regulates age-related muscle decline and sarcopenia

8 months 1 week ago
Sarcopenia, defined as the progressive loss of skeletal muscle mass and function associated with ageing, has devastating effects in terms of reducing the quality of life of older people. Muscle ageing is characterised by muscle atrophy and decreased capacity for muscle repair, including a reduction in the muscle stem cell pool that impedes recovery after injury. Histone deacetylase 11 (HDAC11) is the newest member of the HDAC family and it is highly expressed in skeletal muscle. Our group...
Renato Odria

SIRT2 suppresses aging-associated cGAS activation and protects aged mice from severe COVID-19

8 months 1 week ago
Aging-associated vulnerability to coronavirus disease 2019 (COVID-19) remains poorly understood. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected aged mice lacking SIRT2, a cytosolic NAD^(+)-dependent deacetylase, develop more severe disease and show increased mortality, while treatment with an NAD^(+) booster, 78c, protects aged mice from lethal infection. Mechanistically, we demonstrate that SIRT2 modulates the acetylation of cyclic GMP-AMP synthase...
Marine Barthez

Fibril fuzzy coat is important for α-synuclein pathological transmission activity

8 months 1 week ago
α-synuclein transmission and propagation are hallmarks of synucleinopathies, yet the molecular mechanisms remain elusive. Using α-synuclein preformed fibrils as pathological seeds, we observed a gradual decline in neuronal transmission activity during serial propagation. Fibril polymorphisms were identified from the initial generation: mini-P, with higher neuronal seeding activity, and mini-S, which accelerated recombinant α-synuclein aggregation. Changes in their proportions during propagation...
Yuliang Han

Reevaluating Alzheimer's disease treatment: Can phytochemicals bridge the therapeutic Gap?

8 months 1 week ago
Alzheimer's disease (AD) is a growing neurological disorder giving impact cognition and memory, posing a global health challenge with over 55 million individuals affected. It is the 7th foremost cause of dying worldwide, and its pervasiveness is expected to twofold in each five years, reaching 115 million by 2050. AD is characterized by neurofibrillary tangles, senile plaques, and oxidative stress, leading to synaptic failure and cognitive decline. Currently, there is no cure, and available...
Kishor Kumar Roy