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A study could transform the lab study of olfaction—and may challenge a Nobel-winning hypothesis

Low bone mass is frequently observed in Alzheimer's disease (AD), yet the underlying mechanisms remain poorly understood. In this study, we demonstrate that sensory nerves constitute a critical component of the skeletal stem cell (SSC) niche. Deletion of the neurotrophin receptor p75NTR in neurons or sensory-specific cells, but not in osteogenic or sympathetic cells, resulted in reduced sensory innervation, disrupted SSC homeostasis, and significant bone loss. Although a cell-intrinsic role of...

CONCLUSIONS AND IMPLICATIONS: The established PhA cutoff values can be integrated into routine health assessments, enabling early detection and targeted interventions that could improve the quality of life of this population.

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Solid-state lithium diffusion dynamics are critical for the rate capability and longevity of Li-ion batteries. Conventionally, nanoscale lithium diffusion within individual battery particles has been simplified as being primarily driven by concentration gradients, despite the associated processes inducing local lattice expansion, contraction, and strain fields. Using operando scanning transmission soft X-ray microscopy with high spatial resolution and chemical sensitivity to track nanoscale...

WNT signaling is an essential pathway regulating tissue morphogenesis and regeneration. However, harnessing the pathway for regenerative medicine has been challenging due to the lack of approaches to identify and deliver specific WNT ligands to the target tissue. Herein, we reported that WNT and R-spondin (RSPO) proteins could be transported on engineered exosomes and activate the pathway synergistically. We showed that WNT3A and RSPO1 co-treatment could effectively regulate hepatic cell fate...

Cellular senescence, a hallmark of aging, can be quantified by the gene expression composite scores for the canonical senescence pathway (CSP), senescence initiating pathway (SIP), senescence response pathway (SRP), a summary of the three, and the SenMayo gene list; however, these have not been probed in representative populations. Using RNA sequencing data from the U.S. representative Health and Retirement Study (HRS) sample (N = 3580), we examine how these composite scores relate to...

Epigenetic clocks are emerging as promising tools for examining social and health disparities. These measures are typically developed using blood DNA methylation (DNAm) data. Cheek swabs, being less invasive than blood collection, can be used to assay buccal DNAm. This study examines how buccal-originated epigenetic clocks relate to socioeconomic status (SES) and health, and compares these associations to those of blood-originated clocks applied to buccal DNAm in the German SOEP cohort (N =...

Sarcopenia is a major contributor to frailty and functional decline among older adults. Combining exercise with nutritional strategies such as creatine monohydrate (CRE) and β-hydroxy-β-methylbutyrate (HMB) supplementation may help to preserve strength and independence. To evaluate the effects of 6-week CRE + HMB supplementation combined with an integral physical conditioning (IPC) program on functional strength and body composition in physically active older adults. In a randomized,...

CONCLUSIONS: Among older adults, the risk of all-cause mortality significantly increased with a more rapid progression of tooth loss, regardless of baseline tooth count. These findings emphasize the critical importance of monitoring tooth loss progression.

Age-related proteinopathies, including Alzheimer's and Parkinson's disease, are driven by toxic accumulation of misfolded and intrinsically disordered proteins (IDPs) that overwhelm cellular proteostasis. The proteasome clears these proteins, but its failure in disease remains unclear. We engineered a Caenorhabditis elegans model with a hyperactive 20S proteasome (α3ΔN) for selective 20S activation. α3ΔN markedly enhanced IDP and misfolded protein degradation, reduced oxidative damage, and...

Extracellular vesicles present a promising alternative to stem cells in regenerative medicine and gerontology. They offer significant advantages over cell transplantation, demonstrating potential for slowing aging and treating age-related diseases. Extracellular vesicles secreted by diverse cell types modulate inflammation, stimulate tissue regeneration, and exhibit anti-inflammatory and immunomodulatory properties. This work explores the therapeutic potential of extracellular vesicles as...

Pathogens are major drivers of cancer globally and the processes of infection and carcinogenesis unfold over decades making them difficult to observe in human or natural populations. We investigate these hidden dynamics for the foodborne trematode Opisthorchis viverrini, which is a primary cause of biliary cancer (cholangiocarcinoma) and infects 12 million people in Southeast Asia. In tumors from patients exposed to O. viverrini, we find that the earliest chromosomal amplifications carrying...

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