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New obesity discovery rewrites decades of fat science

2 weeks 3 days ago
Scientists have uncovered a surprising secret hidden inside fat cells that could reshape how we think about obesity and metabolic disease. A protein called HSL, long believed to simply release stored fat when the body needs energy, turns out to have a second job deep inside the nucleus of fat cells—helping keep those cells healthy and balanced. Even more surprising, people and mice missing this protein don’t become obese as expected; instead, they lose fat tissue in a dangerous condition called lipodystrophy.

A common constipation drug shows surprising power to protect kidneys

2 weeks 4 days ago
A common constipation drug may have unexpectedly unlocked a new way to slow chronic kidney disease — a condition that affects millions and often leads to dialysis. In a clinical trial involving 150 patients, researchers found that lubiprostone, a medication normally used to treat constipation, helped preserve kidney function in people with moderate CKD. Scientists traced the effect to changes in gut bacteria that boosted production of spermidine, a compound linked to healthier mitochondria and reduced kidney damage.

Lipid dysregulation as a central contributor of neurodegenerative diseases: Emerging therapeutic targets and strategies

2 weeks 4 days ago
Lipid homeostasis is essential for preserving the structural integrity and functional capacity of the brain. A diverse array of lipids, including cholesterol, phospholipids, and sphingolipids, has been identified as playing pivotal roles. Dysregulation of lipid metabolism is increasingly recognized as a central pathological mechanism in neurodegenerative diseases, including Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Huntington's Disease, and Cerebrotendinous...
Jiajie Zhang

Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons

2 weeks 4 days ago
Genome-wide association studies (GWAS) have identified APOE2 allele as linked to exceptional longevity, with carriers exhibiting a reduced risk of Alzheimer's disease (AD). Apolipoprotein E (APOE), a glycoprotein involved in lipid transport, has three major alleles. However, alterations in lipid metabolism alone do not fully explain APOE2's protective effects. In contrast, APOE4 is the strongest genetic risk factor for AD. To investigate how APOE2 promotes neuronal longevity and confers...
Cristian Gerónimo-Olvera

Trehalase-trehalose axis in the human brain: A potential modulator of neuroprotection and neurodegeneration

2 weeks 4 days ago
Trehalase, the primary enzyme responsible for the degradation of gastrointestinal trehalose ("mushroom sugar"), is well-characterised in the human gut, but has not been conclusively identified in the human brain. Trehalose itself has shown promise in neuroprotection through diverse molecular mechanisms, including the autophagy-driven clearance of cellular debris and neurotoxic aggregates. However, the mechanisms activating trehalose and its integration into human central nervous system processes...
Kalle Keisu

Muscle-derived Mimecan regulates hypothalamus-brown adipose tissue communication and promotes health and lifespan in mice

2 weeks 4 days ago
Inter-organ communication plays a critical role in mammalian aging and longevity control. Here, we identified Mimecan from transcriptomic comparisons between young and aged skeletal muscles. Skeletal muscle-derived Mimecan regulates core body temperature via brown adipose tissue (BAT), which is impaired in aged mice. Skeletal muscle-specific loss- and gain-of-function models demonstrate that Mimecan activates melanocortin 4 receptor (MC4R)-positive neurons in the dorsomedial hypothalamus (DMH)...
Kentaro Mori

Garlic-derived metabolite activates LKB1, promotes adipose eNAMPT secretion, and improves age-related muscle function via hypothalamic signaling

2 weeks 4 days ago
Garlic (Allium sativum L.) and its aged extract contain many bioactive compounds that can bring health benefits to humans. Among them, S-1-propenyl-L-cysteine (S1PC) has recently drawn significant attention in the field of nutriceutical research. However, the mechanism of its molecular action has remained poorly understood. Here, we show that S1PC significantly activates liver kinase B1 (LKB1) through enhancing its tertiary complex formation with STRAD and MO25, leading to stimulating the...
Jun-Ichiro Suzuki

Gut microbial signatures for aging-related sarcopenia and dietary links among community-dwelling old-old adults: A metagenomic study

2 weeks 4 days ago
CONCLUSION: In old-old adults, we identified distinct gut microbiota signatures associated with sarcopenia. R. lactatiformans and P. faecium emerged as candidate features. The dietary-microbiota correlations suggest potential nutrition strategies. These findings provide a basis for exploring microbiota-based approaches in advanced aging.
Ting Zhang

Exceptional Longevity Modifying Allele APOE2 Promotes DNA Signaling Pathways Resisting Cellular Senescence in Human Neurons

2 weeks 4 days ago
Genome-wide association studies (GWAS) have identified APOE2 allele as linked to exceptional longevity, with carriers exhibiting a reduced risk of Alzheimer's disease (AD). Apolipoprotein E (APOE), a glycoprotein involved in lipid transport, has three major alleles. However, alterations in lipid metabolism alone do not fully explain APOE2's protective effects. In contrast, APOE4 is the strongest genetic risk factor for AD. To investigate how APOE2 promotes neuronal longevity and confers...
Cristian Gerónimo-Olvera

Liquid-derived, solvent-free vapor-mediated dimensional reconstruction yields a record fill factor in inverted perovskite solar cells

2 weeks 4 days ago
Despite recent advances, the fill factor (FF) of perovskite solar cells remains limited, largely owing to defect-related recombination. Paradoxically, most defect passivation approaches still depend on solvents, which deteriorate stability and pose challenges for large-scale fabrication. Here, we introduce a vapor-phase deposited from a liquid triethylammonium pentafluoropropionate (TEA-PFP) layer on top of perovskite. During deposition, TEA⁺ reacts with residual PbI(2) to generate a...
Yinjiang Liu

Circulating levels of insulin-like growth factor binding protein 7 are associated with risks of chronic diseases and death

2 weeks 4 days ago
Relationships between the concentration of circulating IGFBP-7 and risk of disease and mortality have been suggested by small-scale investigations. In this prospective study, we investigated these relationships among 53,003 UK Biobank participants. Higher IGFBP-7 level was significantly associated with increased risk for liver cancer, all-cause mortality, diabetes, and other diseases. Associations were robust across sex and age groups and persisted over long follow-up. IGFBP-7 polygenic risk...
Zhi Li

Calibrating T cell responsiveness through interactions with self

2 weeks 4 days ago
During an immune response, T cells face one of the most consequential decisions of their lifespan upon recognition of a ligand they have not previously encountered: whether to exit the naive basal state, undergo clonal expansion and acquire effector functions. This process is often portrayed as a binary switch, in which naive cells from a highly diverse repertoire transition from an 'off' state to an 'on' state. However, this digital view overlooks the crucial prior information that T cells...
Judith N Mandl

High-resolution glutamate-weighted mapping of in vivo mouse brain across age with chemical exchange saturation transfer MRI

2 weeks 4 days ago
Aging in the mammalian brain involves significant structural, functional, and metabolic changes, including a decrease in glutamate concentration. Glutamate-weighted chemical exchange saturation transfer (gluCEST) MRI provides a non-invasive method for mapping glutamate distribution with high spatial resolution. Collecting data from a large cohort of healthy mice aged 2 to 23 months, scanned in vivo at 17.2 T, we demonstrate that gluCEST can differentiate multiple brain regions, and introduce a...
R Gaudin

Comparing Cognitive-Motor Interference Across Younger, Middle-Aged, and Older Adults During Dual-task Walking

2 weeks 4 days ago
CONCLUSION: Age-related differences in CMI were more prominent for gait than for memory tasks. Findings support that DT performance incrementally declines with age. Middle-aged and older adults had similar gait destabilization in different DT walking demands, but older adults had higher interference with DT walking of auditory processing demands. Retrieval tasks during walking expose early deficits in middle-aged adults that differentiate them from younger adults. Results further suggest...
Shatha Abdulaziz Aldraiwiesh

Targeting Hyperoxia-Induced Cellular Senescence in Developing Human Airway Cells: Senomorphics Versus Senolytics Versus Antioxidants

2 weeks 4 days ago
Supplemental oxygen (hyperoxia), often provided to premature infants, can disrupt lung growth and contribute to development of neonatal and pediatric lung diseases, necessitating understanding of underlying mechanisms. We previously showed that even moderate hyperoxia (< 60% O(2)) induces detrimental cellular senescence in 18-22 weeks human fetal airway smooth muscle (fASM), a key cell type in airway contractility and remodeling. In this study, we examined the ability of senotherapeutics...
Maunick Lefin Koloko Ngassie

Epigenetic age acceleration measures and chemotoxicity in older adults with early breast cancer

2 weeks 4 days ago
Among older adults with early breast cancer, the risk of chemotoxicity can vary widely despite similar chronological age. Here, we evaluated whether epigenetic indicators of biological age can stratify the risk of chemotoxicity in this population. In a prospective study of 394 women age > 65 with stage I-III breast cancer treated with neo/adjuvant chemotherapy, we analyzed peripheral blood DNA methylation patterns to estimate epigenetic age acceleration (EAA) before chemotherapy. We tested five...
Jingran Ji