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In the AI era, coding means thinking like a systems architect
The histone variant H2A.Z regulates sex differences in Alzheimer's disease pathophysiology
Alzheimer's disease (AD) disproportionately affects women, yet mechanisms underlying this sex difference remain unclear. Histone variants are overrepresented components of aging neuronal chromatin, but their contribution to AD is unknown. Here, we identify the histone variant H2A.Z as a sex-specific regulator of AD in the postmortem human hippocampus and in 5xFAD mice. H2A.Z occupancy decreased in female but increased in male AD patients. In females, reduced H2A.Z occupancy at the transcription...
EXERCISE, DNA METHYLATION, AND ALZHEIMER'S DISEASE: MECHANISTIC LINKS AND FUTURE DIRECTIONS IN INTERGENERATIONAL RESEARCH
Alzheimer's disease (AD) is the most common cause of dementia and remains without a cure; recently introduced disease-modifying therapies provide only modest slowing in selected patients. Physical exercise is associated with better cognitive and functional outcomes, but the molecular mechanisms underlying these benefits remain incompletely understood. DNA methylation is a potential interface linking environmental stimuli to gene regulation and neural function. This narrative review examines...
Humanin attenuates neuronal cellular senescence and preserves neurotransmitter release in differentiated PC12 cells
Cellular senescence, characterized as a permanent arrest of cell proliferation, is triggered by various types of stress. Senescent cells are identified by markers, including senescence-associated β-galactosidase (SA-β-gal) activity and the secretion of senescence-associated secretory phenotype (SASP) factors. These senescent phenotypes have been observed in neurons, suggesting that cellular senescence may contribute to the pathogenesis of neurodegenerative diseases. Humanin (HN), an endogenous...
The histone variant H2A.Z regulates sex differences in Alzheimer's disease pathophysiology
Alzheimer's disease (AD) disproportionately affects women, yet mechanisms underlying this sex difference remain unclear. Histone variants are overrepresented components of aging neuronal chromatin, but their contribution to AD is unknown. Here, we identify the histone variant H2A.Z as a sex-specific regulator of AD in the postmortem human hippocampus and in 5xFAD mice. H2A.Z occupancy decreased in female but increased in male AD patients. In females, reduced H2A.Z occupancy at the transcription...
Integrated Mechanisms of the Gut-X Axis and Multi-Organ Injury in Sepsis
Sepsis is a life-threatening syndrome defined by infection-triggered dysregulation of the host response, and its persistently high mortality and marked clinical heterogeneity remain major barriers to early risk stratification and individualized management. While the gut is increasingly recognized as a key modulator of the systemic sepsis response, current evidence does not support a universal, upstream causal role for intestinal alterations in the initiation of multi-organ injury. In this...
Cellular Senescence in Heart Failure with Preserved Ejection Fraction: Mechanisms and Therapeutic Opportunities
Heart failure with preserved ejection fraction (HFpEF) contributes to nearly 50% of the global heart failure (HF) cases, and remains a major clinical challenge because of its heterogeneous pathophysiology, substantial residual morbidity, and limited mechanism-based treatment options. HFpEF is increasingly recognized as a heterogeneous multisystem syndrome closely associated with aging, cardiometabolic comorbidities, and chronic low-grade inflammation. Cellular senescence and the...
Humanin attenuates neuronal cellular senescence and preserves neurotransmitter release in differentiated PC12 cells
Cellular senescence, characterized as a permanent arrest of cell proliferation, is triggered by various types of stress. Senescent cells are identified by markers, including senescence-associated β-galactosidase (SA-β-gal) activity and the secretion of senescence-associated secretory phenotype (SASP) factors. These senescent phenotypes have been observed in neurons, suggesting that cellular senescence may contribute to the pathogenesis of neurodegenerative diseases. Humanin (HN), an endogenous...
Does perturbed adaptive myelination contribute to cognitive dysfunction in Alzheimer's disease?
The consequences of oligodendrocyte involvement in Alzheimer's disease are poorly understood. Could a key role of gray-matter oligodendrocytes-activity-dependent adaptive myelination to sustain changes in activity-be perturbed, leading to cognitive loss?
Shedding light on left hippocampal mGlu5 in Alzheimer's disease
Metabotropic glutamate receptor 5 (mGlu5) is essential for synaptic plasticity and memory, making it a potential therapeutic target in Alzheimer's disease (AD). While hemispheric asymmetries in hippocampal function have been observed in AD patients, the lateralized contribution of mGlu5 signaling to cognitive decline remains unclear. Here, we show a physiological left-right asymmetry in hippocampal mGlu5 expression in wild-type mice, with higher levels in the left hemisphere, consistent with...
In mice, a population of male germ cells show characteristics of nonapoptotic cell death during G0 arrest
In mammals, a small population of spermatogonial stem cells (SSCs) is established shortly after birth. These cells self-renew and produce sperm for the male's reproductive lifespan, passing the genome on to the next generation. Establishment of a population of SSCs with high genomic integrity is essential. SSCs are derived from a much larger precursor population of male germ cells (MGCs) that differentiate during fetal life. During the last third of gestation, MGCs undergo a prolonged period of...
Appetite Loss, Inflammation, and Incident Functional Loss Among Community-Dwelling Older Adults
CONCLUSION: Impaired appetite and increased inflammatory biomarkers are independently linked to mobility loss. Appetite impairment might signal early nutritional and supportive care needs, but inflammation-targeted interventions require further study.
Robust and replicable effects of ageing on resting-state brain electrophysiology measured with MEG
Non-invasive recordings of brain electrophysiology provide credible insights into decline in neuronal functioning with age. New approaches are required to translate these results into compelling clinical metrics and meet the global challenge of preserving brain health in ageing. Changes in neuronal dynamics with ageing are observable in the power spectra of EEG and MEG recordings. Highly promising candidates for electrophysiological markers have been identified, but progress is hindered by...
Crosstalk Between the NRF2 Signaling Pathway and Heat Shock Proteins: Implications for Cellular Stress Response and Disease Therapy
Cells are continuously exposed to oxidative and proteotoxic stress that disrupt redox balance and protein homeostasis. Two major cytoprotective systems-the nuclear factor erythroid 2-related factor 2 (NRF2) pathway and the heat shock response (HSR) mediated by heat shock factor 1 (HSF1) and heat shock proteins (HSPs)-form an interconnected stress-adaptation network that coordinates redox defense, proteostasis, and cellular survival. Although historically viewed as largely independent pathways,...
Popular weight loss drugs linked to a surprising fingernail problem
Popular GLP-1 weight loss drugs, such as Ozempic and Wegovy, have been linked to unexpectedly high rates of nail detachment, hair loss, and scalp inflammation, with some problems occurring several times more frequently among users. Researchers found that weight loss alone could not fully explain the differences, suggesting there may be more to these overlooked symptoms.
Scientists find hidden driver of aging and a simple amino acid that fights memory loss in mice
Scientists discovered that declining levels of a protein called Menin may help drive aging, and restoring it in older mice reversed several age-related changes in just 30 days. Even more surprisingly, supplementing with a simple amino acid called D-serine improved memory and learning, offering a potential new approach to age-related cognitive decline.
Did an AI or a human write that paper? New detector decides by examining its ideas
Algorithm looks for clues about a paper's origin that text-based detectors miss