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Repressor Element 1-Silencing Transcription factor (REST) emerges as a metabolism-sensitive transcriptional hub that supports basal mitophagy, mitochondrial quality, and synaptic function in neurons. In Alzheimer's disease, REST becomes mislocalized and functionally impaired, coinciding with early defects in mitochondrial quality control. Activation of the NAD^(+) -SIRT1 axis enhances REST nuclear activity, restores its mitochondrial and neuroprotective gene programs, and attenuates pathological...

CONCLUSIONS: The UMNs of the older adults and the potential threat to inequalities require the attention of policymakers. Interventions should focus on improving access to medical services, with a particular emphasis on addressing the needs of vulnerable populations.

No abstract

The incidence of neurodegenerative diseases, including Alzheimer's disease (AD), continues to increase with the extension of human lifespan. However, their pathogenesis remains incompletely understood. Altered energy metabolism, particularly glucose metabolism involving glycolysis and oxidative phosphorylation, is widely recognized as an early pathological feature of neurodegenerative diseases. Astrocytes, the most numerous and widely distributed functional cells in the central nervous system...

A surprising discovery is reshaping scientists' understanding of how humans develop sharp central vision before birth. Instead of blue cone cells migrating away from the retina's center, the study found they transform into red and green cones under the influence of vitamin A-related signals and thyroid hormones. The findings could improve lab-grown retinal tissue and lay the groundwork for future cell therapies to restore vision lost to age-related eye diseases.

Poison control calls involving semaglutide (Ozempic and Wegovy) soared after the drug was approved for weight management, with researchers linking the increase to accidental dosing mistakes rather than intentional misuse. Simple education about proper weekly dosing and gradual dose increases could help prevent many of these avoidable incidents.

Scientists have created a silicon chip that can write dozens of DNA sequences simultaneously using electricity and water-based enzymes, offering a cleaner alternative to conventional DNA manufacturing. The breakthrough could eventually support portable DNA-writing devices and even massive DNA data storage, although new chemistry will be needed to scale the technology further.

Tiny silica nanoparticles engineered to seek out prostate cancer caused tumor cells to self-destruct and supercharged the immune system in preclinical mouse studies. Combined with immunotherapy, the treatment produced complete remissions in multiple mice, raising hopes for a powerful new approach to prostate cancer.

Researchers have cracked the code behind bacteria's ability to naturally manufacture multiple versions of powerful anti-cancer drugs. The discovery could make it much easier to engineer new cancer treatments inspired by nature, including improved versions of existing medicines.

Three approaches—including one that exploits Earth’s radiation belts—could help enforce ban on orbital nuclear weapons

Chronic neuroinflammation is a defining feature of brain ageing and neurodegenerative disorders, yet the molecular mechanisms responsible for its persistence remain incompletely understood. Although autophagy dysfunction, glial senescence, and inflammasome activation are well-established contributors to progressive neurodegeneration, these processes are often analysed independently or through pairwise interactions, leaving their collective contribution to persistent neuroinflammation and disease...

CONCLUSION: Disrupted brain RAS homeostasis induces pro-inflammatory microglial remodeling and worsens PD neurodegeneration. This study reveals novel pathogenic mechanisms and identifies promising therapeutic targets for PD treatment.

Age-related macular degeneration (AMD) is a degenerative retinal disease initiated by dysfunction of the retinal pigment epithelium (RPE), in which age-related mitochondrial impairment, oxidative stress, chronic inflammation, and complement activation collectively drive outer retinal dysfunction and RPE atrophy, ultimately leading to progressive central vision loss. Accumulating evidence indicates that mitochondrial abnormalities, including excessive reactive oxygen species (ROS) production,...

Alzheimer's disease (AD) is characterized by neuroinflammation, yet the impact of concurrent systemic infections on the AD brain remains poorly understood. We investigated the molecular mechanisms underlying the central nervous system response to systemic infections in AD by analyzing RNA sequencing data generated in the prefrontal cortex from 202 post-mortem donors (113 AD, 89 controls), where we stratified by the presence of a respiratory infection at the time of death. We identified 763...

CONCLUSION: Based on our data, GrimAgeAcc is associated with ARHL and systemic age-related diseases (dementia, CVD, diabetes), potentially through shared biological pathways (e.g., endocytosis, lysosomal, inflammatory). Chronological age explains 28-50% of these associations, yet ARHL remains independently associated with all three outcomes after age adjustment. The cochlea may be vulnerable, but causal evidence is lacking. All findings are hypothesis-generating and require experimental...

Chronic neuroinflammation is a defining feature of brain ageing and neurodegenerative disorders, yet the molecular mechanisms responsible for its persistence remain incompletely understood. Although autophagy dysfunction, glial senescence, and inflammasome activation are well-established contributors to progressive neurodegeneration, these processes are often analysed independently or through pairwise interactions, leaving their collective contribution to persistent neuroinflammation and disease...

Frailty is a multifactorial geriatric condition linked to increased mortality and adverse health outcomes and is associated with gut microbiome features that differ from those observed in healthy ageing. We analyze gut metagenomic profiles in relation to estimated frailty severity and frailty-related clinical outcomes assessed with an internally developed and validated Frailty Mortality Index (FMI) in the SUPERB cohort, comprising 2,081 Swedish women aged 75-80 years. The FMI is a composite...

We examined the associations of reproductive behaviors and genetic susceptibility with aging indicators among female participants in the UK Biobank. Reproductive behaviors included the number of children ever born (NEB), age at first birth (AFB), age at last birth (ALB), and span of years of births (SYB). Aging indicators included frailty, PhenoAge acceleration, KDM-BA acceleration, and brain age difference (BrainAGE-diff). In multivariable analyses, reproductive behaviors showed nonlinear...

Neural circuits must remain functionally stable while adapting to changing demands and levels of stress. While this balance is thought to rely on plasticity programs integrating molecular and activity-dependent signals, mechanistic models of how such adaptations are orchestrated remain limited. Here, we show that impairment of autophagy in the Drosophila mushroom body (MB) induces brain-wide, post-transcriptional remodeling of presynaptic active zones, characterized by increased expression...