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DNA methylation (DNAm) plays a critical role in Alzheimer's disease (AD). Previous epigenome-wide association studies using 450K arrays captured limited CpG coverage and often focused on a single neuropathological measure. Here we profiled DNAm in 1,250 postmortem prefrontal cortex samples from the Rush Alzheimer's Disease cohorts using the Infinium MethylationEPIC v2 array (~930,000 CpGs) and performed epigenome-wide association studies of multiple neuropathologic measures, including AD...

Cognitive impairment affects 30%-80% of patients with heart failure, yet the mechanisms beyond reduced brain blood flow remain poorly defined. Here we show that circulating factors released during heart failure trigger senescence of brain blood-vessel endothelial cells, which in turn drives synaptic loss and cognitive decline through crosstalk between endothelial cells and microglia, the brain's immune cells. Using a pressure-overload model (transverse aortic constriction) combined with plasma...

Chronic social deficits (persistent feelings of being lonely or isolated) have been linked to premature mortality, yet the underlying physical and mental pathways remain unclear. This study used data from 4,090 older adults in the English Longitudinal Study of Ageing, a longitudinal panel study. Using outcome-wide analyses, we assessed how the chronicity of social deficits was associated with 17 health outcomes across physical, mental, cognitive and behavioural health domains. Regression models...

The buried interface between the charge transport layer and the overlying perovskite absorber is critical yet difficult to probe in perovskite solar cells. Because light enters through the transparent substrate and is predominantly absorbed near this region, photo-induced degradation processes are partially initiated at the hidden buried interface. Here, we reveal that instability at the buried SnO(2)/perovskite interface triggers structural and chemical decomposition of the perovskite layer. To...

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...

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...

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...

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...

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...

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...

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 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?

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 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...

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.

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...

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 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 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.