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The expanding role of the NLRP3 inflammasome from periodic fevers to therapeutic targets

2 months ago
Understanding and treating inflammation has proven a formidable challenge. The initiator and central motor of inflammation, the protein NLRP3, is an innate immune sentinel and nonspecific sensor of cellular perturbation. A wide array of inflammatory triggers prompts the formation of an NLRP3 'inflammasome' complex, leading to inflammatory interleukin-1 family cytokine release and pyroptotic cell death. Since gain-of-function mutations in NLRP3 were demonstrated to cause a rare autoinflammatory...
Alexander N R Weber

Non-histone lysine lactylation: Emerging roles in tumor biology and therapeutic implications

2 months ago
Lactate, a byproduct of glycolysis, was first identified to induce a novel post-translational modification (PTM) known as lysine lactylation (Kla) in 2019. Kla has been shown to regulate various biological processes, including transcription, metabolism, cell proliferation, and inflammatory responses, which are pivotal in both tumorigenesis and cellular aging. Initially, Kla was identified as an epigenetic marker on histones, where it regulates gene transcription. However, more recent studies...
Qu Zhang

Effects of resistance training on osteosarcopenia in community-dwelling postmenopausal Korean women: Randomised controlled ERTO-K trial

2 months ago
CONCLUSIONS: A 6-month program of progressive resistance exercise combined with nutritional support improved muscle mass and strength in postmenopausal women with osteosarcopenia. Although the HE group showed less improvement at earlier time points, their muscle strength and physical performance were comparable to those of the RE group by the end of the intervention.
Byung Chan Lee

Epigenetic age acceleration and midlife cognition: joint evidence from observational study and Mendelian randomization

2 months ago
The relationship between epigenetic age acceleration (EAA) and midlife cognitive function remains unclear, with limited causal evidence. We investigated this association in 1252 Black and White middle-aged adults from the Bogalusa Heart Study (BHS) and conducted a two-sample Mendelian randomization (MR) analysis using GWAS summary statistics for EAA (N = 34,710) and cognition (N ≤ 106,162). In BHS, higher Hannum age acceleration, PhenoAge acceleration, and GrimAge acceleration (GrimAA) were each...
Yang Pan

Adaptive loss of shortwave-sensitive opsins during cartilaginous fish evolution

2 months ago
Cartilaginous fishes (e.g., sharks, rays, and skates) cannot see blue or violet light, potentially because they lack the shortwave-sensitive cone opsin gene (sws). Widespread gene loss can occur during evolution, but the evolutionary mechanisms underlying sws loss remains unclear. Here, we construct whole-genome assemblies of Okamejei kenojei (skate) and Prionace glauca (blue shark). We then analyze the distribution characteristics and intragroup differences of opsin-related genes in...
Bo Zhang

Noncanonical function of Pannexin1 promotes cellular senescence and renal fibrosis post-acute kidney injury

2 months ago
Acute kidney injury (AKI) can lead to chronic kidney disease (CKD), a transition driven by cellular senescence, a state of irreversible cell-cycle arrest. However, the molecular mechanisms promoting this pathological process remain unclear. Here we show that the channel protein Pannexin1 (Panx1) promotes this detrimental senescence and subsequent kidney fibrosis. We found that Panx1 functions in a noncanonical role as a calcium (Ca^(2+)) leak channel within the endoplasmic reticulum (ER), a key...
Liuwei Huang

Direct and bisulfite-free 5-methylcytosine and 5-hydroxymethylcytosine sequencing at single-cell resolution with scTAPS and scCAPS + 

2 months ago
We present direct sequencing methodologies, scTAPS for 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) and scCAPS + specifically for 5hmC, enabling quantitative detection of 5mC and 5hmC at single-base resolution and single-cell level. Achieving approximately 90% mapping efficiency, our plate-based methods accurately recover 5mC and 5hmC profiles in CD8 + T and mouse embryonic stem cells. Notably, scCAPS + reveals a global increase in 5hmC across neuronal and non-neuronal cells in the...
Xiufei Chen

Uncovering the link between incidental physical activity and inhibition of automatic responses in aging. An ERP study

2 months ago
The concept of cognitive reserve explains how the brain maintains function despite age-related changes or neuropathological damage. Factors such as education, cognitive stimulation, and physical activity contribute to strengthening this reserve. While research has highlighted the benefits of structured exercise, less attention has been given to the impact of incidental physical activity (IPA) everyday, unplanned movements like walking or household chores. This study examined the relationship...
Javier Sanchez-Lopez

Difference between Okinawan and Dutch older adults in prefrontal brain activation

2 months ago
CONCLUSION: Our results reveal less activation of the task-relevant areas in participants from Okinawa as compared to Dutch participants. It could be hypothesized, with caution, that Okinawan older adults may need less executive processing resources to perform the task. Other differences in activation may be related to different strategy use, which may be studied in more detail in future investigations.
Branislava Ćurčić-Blake

Patterns of transcriptomic aging in the hippocampus of rhesus macaques highlight midlife transitions

2 months ago
Patterns of brain aging are generally conserved among primates; however, there is marked variation in the observed rate among individuals, species, and brain regions. The hippocampus is a region particularly susceptible to the aging process. To better understand how the hippocampus changes over the lifespan, we measured gene expression in 96 banked hippocampus samples from adult male and female rhesus macaques aged 3-35 years old. Importantly, our dataset included representation across adulthood...
Tanner J Anderson

Environmental NaCl affects Caenorhabditis elegans development and aging

2 months ago
Sodium chloride (NaCl) is an essential nutrient, but it is toxic in excess. In humans, excessive dietary NaCl can cause high blood pressure, which contributes to age-related diseases, including stroke and heart disease. We used Caenorhabditis elegans to elucidate how NaCl levels influence animal aging. Most experiments on this animal are conducted in standard culture conditions: Nematode Growth Medium (NGM) agar with a lawn of E. coli. Here, we report that the supplemental NaCl in standard NGM,...
Franziska Pohl