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Disruption of proteostasis is a hallmark of aging. Given that cellular resources are limited, this necessitates a coordinated orchestration of different proteostatic subsystems. Yet, the principles governing this process, including the potential role of trade-offs, are not well defined. Here, we report a trade-off between the endoplasmic reticulum unfolded protein response (UPR^(ER)) and the cytosolic UPR (UPR^(cyto)) in C. elegans that influences lifespan. We find that wild-type animals...

DNA methylation-based epigenetic clocks have been highlighted as promising biomarkers of ageing, and they have been shown to robustly predict morbidity and mortality. However, current literature is lacking a formal analysis of the increased prediction accuracy, or the added value, of the epigenetic clocks over traditional risk factors, such as body composition, smoking, or alcohol consumption, in predicting common chronic diseases. Here, we have compared the most commonly used epigenetic clocks...

Aging is accompanied by widespread remodeling of DNA methylation (DNAm), which can be leveraged to build epigenetic clocks. In mice, most DNAm clocks rely on internal organs or terminal tissues, limiting longitudinal studies. Here, we compared age-associated DNAm patterns in matched blood and tail-an easily accessible but underexplored tissue-and evaluated both as substrates for tissue-specific DNAm age prediction. Matched blood and tail were collected from male C57BL/6N Per2::Luc mice aged...

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...

Science, Ahead of Print.

Science, Ahead of Print.

Science, Ahead of Print.

Science, Ahead of Print.

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.