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Researchers have identified a new Alzheimer’s target and created an experimental compound that blocks a damaging process inside brain cells. In mice, the treatment slowed nerve cell loss, reduced Alzheimer’s-related changes, and even appeared to promote healthier aging.

Scientists have uncovered a key brain signal that helps us break old habits and adapt when circumstances suddenly change. By watching mice navigate a virtual maze, researchers found that disappointment—when an expected reward failed to appear—triggered a surge of the neurotransmitter acetylcholine, making the animals more likely to try a new strategy. When acetylcholine was blocked, the mice became less flexible and were more likely to stick with outdated choices.

Lewy bodies, the defining pathological feature of Parkinson's disease, are intraneuronal inclusions enriched in aggregated alpha-synuclein (αSyn). We used correlative light and electron microscopy to selectively investigate phosphorylated αSyn (αSyn^(pS129))-positive inclusions in the substantia nigra of end-stage postmortem Parkinson's disease brain. Here we show that somatic αSyn^(pS129) inclusions in nigral dopaminergic neurons are consistently fibrillar, whereas the membranous-type...

An increasing number of studies indicate that ferroptosis, a lethal pathway initiated by excessive iron-dependent lipid peroxidation, and pivotal to the survival of dopaminergic neurons and the progression of Parkinson's disease (PD), may be regulated by the lysosomal pathway. Mutation and loss of function of the lysosomal enzyme, glucocerebrosidase, induce the accumulation of glycosphingolipids and alterations in lysosome activity, which have been associated with a higher risk of developing PD....

Neurons and glia work together to dynamically regulate neural circuit assembly and maintenance. In this study, we show that Drosophila exhibit large-scale synapse formation and elimination as part of normal CNS circuit maturation and that glia use conserved molecules to regulate these processes. Using a high-throughput ELISA-based in vivo screening assay, we identify new glial genes that regulate synapse numbers in Drosophila in vivo, including the scavenger receptor ortholog Croquemort (Crq)....

Osteoporosis, a common metabolic bone disorder linked to aging, is often accompanied by muscle degeneration. Muscle Bmal1 disruption in mice has been shown to affect various tissues, including the kidney, lung, and bone, indicating that the muscle molecular clock may influence the physiological homeostasis of multiple organs through systemic circulation. Despite this, the role of the muscle clock in age-related osteoporosis remains unclear. In aged mice, we observed a disruption in the circadian...

Lead exposure remains a significant public health problem, and even within current standards, most individuals have limited means to avoid it. Regulating or removing toxic exposures remains a priority, but complementary nearer-term protections are needed. We previously observed that health insurance coverage attenuated associations of blood lead levels with two DNA methylation-based biomarkers of morbidity and mortality: GrimAge2 and DunedinPoAm. In this study, we evaluated whether healthcare...

α-synuclein (α-syn) aggregation is a hallmark of synucleinopathies, a class of neurodegenerative disorders such as Parkinson's disease (PD). Several lines of evidence indicate the involvement of mitochondria in the disease pathology. Despite extensive study, the link between α-syn aggregation and mechanisms of mitochondrial toxicity remains not fully understood. Using high-resolution imaging with electron microscopy, we examined SH-SY5Y cells exposed to α-syn fibrils vs control cells with a...

Exposure to low levels of environmental challenges, known as hormetic stress, fosters subsequent stress resistance and promotes healthy aging in later life. However, specific mechanisms governing transcriptional reprogramming upon hormetic nutrient stress remain elusive. Here, we identify histone H3 lysine 27 acetylation (H3K27ac) as a crucial driver of transcriptomic adaptation to hormetic fasting. Beyond its immediate function of enhancing lipid catabolism for alternative energy sources,...

CONCLUSION: The updated Brazilian Portuguese version of the CFS demonstrates excellent reproducibility and strong convergent validity in hospitalized older adults. These results support its use as a reliable clinical and research tool for frailty assessment in hospitalized older adults, within the scope of the measurement properties evaluated.

Brain aging is increasingly recognized as a heterogeneous and systems-level process involving dynamic interactions among neuronal, glial, vascular, and immune-associated cell populations. Recent advances in single-cell and spatial omics technologies have revealed diverse cellular aging trajectories, region-specific vulnerabilities, and extensive remodeling of intercellular communication networks across the aging brain. These findings challenge reductionist views of aging and emphasize the...

[This corrects the article DOI: 10.3389/fnagi.2026.1707228.].

The aging bone marrow microenvironment is characterized by chronic low-grade inflammation ("inflammaging"), which disrupts skeletal homeostasis and impairs bone regeneration. However, the stromal-immune crosstalk mechanisms sustaining this pathological state remain poorly defined. Here, transcriptomic analysis identified thrombospondin-1 (Thbs1) as a key upregulated component of the senescence-associated secretory phenotype (SASP) in aged bone mesenchymal stromal cells (BMSCs). We demonstrate...

Kaempferol (KMP) is a dietary compound found in a wide range of foods. The therapeutic capabilities of these foods are associated with the phenolic compounds present in their structures, particularly their antioxidant activity. Remarkable medical care areas linked to KMP include pain relief, anti-aging, antiallergic, anticancer, antidiabetic, anti-inflammatory, antioxidant, antipyretic, central nervous system regulation, wound healing, and hepatoprotective characteristics. KMP has attracted...