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Late-life depression (LLD) arises from the confluence of neurochemical dysfunction, oxidative stress, and neural network disintegration, presenting a formidable therapeutic challenge. Here, we demonstrated that combined vitamin D (Vit D) and L-theanine (L-thea) administration exerts multimodal neurorestorative effects in an aged murine model of unpredictable chronic mild stress (UCMS), addressing the core triad of LLD pathology: dopaminergic decline, redox imbalance, and thalamocortical...

We aimed to assess the validity of predicted repetitions in reserve (RIR) during resistance exercise (RE) in community-dwelling older adults (n = 25; 68 ± 4 yrs.; body mass index [BMI] = 28.1 ± 4.6 kg·m^(-2)). Prior to data collection, participants were familiarized with resistance training as well as with the use of RIR and rating of perceived exertion (RPE). Participants completed a one-repetition maximum (1RM) test in the chest press exercise. The repetitions-to-failure test, used to...

Differential expression analysis is crucial in genomics, yet most methods focus only on mean shifts. Variance shifts in gene expression-especially in cellular signaling and aging-are increasingly recognized as being biologically important. We present QRscore (quantile rank score), a general non-parametric framework that extends the Mann-Whitney test to detect both mean and variance shifts through model-informed weights derived from negative binomial (NB) and zero-inflated NB (ZINB)...

Nuclease-helicase DNA2 is a multifunctional genome caretaker that is essential for cell proliferation in a range of organisms, from yeast to human^(1-4). Bi-allelic DNA2 mutations that reduce DNA2 concentrations cause a spectrum of primordial dwarfism disorders, including Seckel and Rothmund-Thomson-related syndromes^(5-7). By contrast, cancer cells frequently express high concentrations of DNA2 (refs. ^(8-11)). The mechanism that precludes cell proliferation in the absence of DNA2 and the...

Aging is a major risk factor for neurodegenerative diseases associated with protein aggregation, including Huntington's disease and amyotrophic lateral sclerosis (ALS). Although these diseases involve different aggregation-prone proteins, their common late onset suggests a link to converging changes resulting from aging. In this study, we found that age-associated hyperactivation of EPS8/RAC signaling in Caenorhabditis elegans promotes the pathological aggregation of Huntington's disease-related...

While research suggests that playing musical instruments promotes neuroplasticity in professional musicians, it remains unclear whether lifelong music experience benefits brain health in non-professional musicians. This study examined whether playing a musical instrument across the lifespan is associated with (a) altered grey matter (GM) density and (b) neuropsychological functioning in older adults at risk for dementia. Sixty-one individuals aged ≥ 50 years were recruited from a memory clinic....

CONCLUSION: Worse global cognitive function and greater WMHs may collectively increase the risk of suicidal attempts in LLD patients.

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...

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.

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.

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...

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....

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,...

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...

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...

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...

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...