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Path integration impairments reveal early cognitive changes in subjective cognitive decline
Path integration, the ability to track one's position using self-motion cues, is critically dependent on the grid cell network in the entorhinal cortex, a region vulnerable to early Alzheimer's disease pathology. In this study, we examined path integration performance in individuals with subjective cognitive decline (SCD), a group at increased risk for Alzheimer's disease, and healthy controls using an immersive virtual reality task. We developed a Bayesian computational model to decompose path...
Age-related differences in the weighting of kinematic and contextual information during action prediction
INTRODUCTION: Predicting others' behaviors is an essential ability to interact efficiently within the social world. Previous evidence suggests that action prediction entails the integration of incoming sensory information with previous experience and contextual expectations. While it is well known that motor and cognitive functions face age-related changes, research examining how action prediction abilities evolve across the lifespan remains limited.
Glutamate-associated research in Parkinson's disease: a bibliometric analysis
CONCLUSION: Research on PD and glutamate focused on countries with increasing aging. The collaboration of different countries and institutions was conducive to promoting the development of this field. The research hotspots included basal ganglia, oxidative stress, DA, neurons, a-Syn, glutamate receptors, and synaptic plasticity. a-Syn and neuroinflammation may be research directions in the future.
Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females
Female sex, age, and APOE4 genotype are the greatest risk factors for Alzheimer's disease. Using a translational perimenopause mouse model based on human Stages of Reproductive Aging Works (STRAW) criteria, we investigated the impact of APOE genotype on female midlife endocrine aging, peripheral metabolic indicators, brain bioenergetic pathways, mitochondrial function, neuroimmune activation, and myelination. Compared to APOE3 females, APOE4 females exhibited accelerated endocrine aging that was...
Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma
The embryonic transcription factor TBXT (brachyury) drives chordoma, a spinal neoplasm without effective drug therapies. TBXT's regulatory network is poorly understood, and strategies to disrupt its activity for therapeutic purposes are lacking. We developed designed ankyrin repeat proteins that block TBXT-DNA binding (T-DARPins). In chordoma cells, T-DARPins reduced cell cycle progression, spheroid formation, and tumor growth in mice and induced signs of senescence and differentiation....
Deletion of sulfate transporter SUL1 extends yeast replicative lifespan via reduced PKA signaling instead of decreased sulfate uptake
The regulation of cellular metabolism and growth in response to nutrient availability is crucial for cell survival and can significantly impact on lifespan. Central to this regulation is a class of transporters that sense and transport specific nutrients and transduce the signal downstream to control genes responsible for growth and survival. In this study, we identified SUL1, a plasma membrane transporter responsible for regulating the entry of extracellular sulfate in Saccharomyces cerevisiae,...
Role of circadian CLOCK signaling in cellular senescence
The circadian rhythm is a key biological mechanism that aligns organisms' physiological processes with Earth's 24-h light-dark cycle, crucial for cellular and tissue homeostasis. Disruption of this system is linked to accelerated aging and age-related diseases. Central to circadian regulation is the CLOCK protein, which controls gene transcription related to tissue homeostasis, cellular senescence, and DNA repair. Research reveals CLOCK's dual role: in normal cells, it supports rejuvenation by...
UCHL1 alleviates nucleus pulposus cell senescence by promoting chaperone-mediated autophagy antagonizing autophagy-dependent ferroptosis through deubiquitination of HSPA8
Chaperone-mediated autophagy (CMA), a lysosome-dependent protein degradation pathway, plays a pivotal yet poorly understood role in cellular senescence-related degenerative diseases. Our study sheds light on a novel mechanism whereby UCHL1 plays a crucial role in mitigating nucleus pulposus cell (NPC) senescence and intervertebral disc degeneration (IVDD) by activating CMA to counteract autophagy-dependent ferroptosis. Through sequencing analysis of human samples, we identified UCHL1 as a...
GPR65 Functions as a Key Factor of Bone Aging and a Novel Therapeutic Target for Osteoporosis
Osteoporosis (OP) is a metabolic bone disease, characterized by loss of bone mass and destruction of bone microstructure, which has a high incidence of disability. Identification of the key factors of pathogenesis is essential for diagnosis and therapy. In this study, we have identified the proton-sensing receptor GPR65, which is specifically expressed in osteoclasts and is significantly down-expressed in osteoclast differentiation, aging, ovariectomy (OVX)-, and tail suspension (TS)-induced...
Single-Cell Fluorescence Imaging Reveals Heterogeneity in Senescence Biomarkers and Identifies Rapamycin-Responsive Sub-Populations
Cellular senescence is a state of irreversible cell cycle arrest accompanied by a distinctive inflammatory secretory profile known as the senescence-associated secretory phenotype (SASP). While various biomarkers, such as senescence-associated beta-galactosidase (SA-βgal), EdU incorporation, p21 and p16, are used to identify senescent cells, no single biomarker universally defines cellular senescence and current methods often fail to address heterogeneity in biomarker expression levels. This...