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Urolithin A: Potential to enhance autophagic clearance and mitigate neuroinflammation in Alzheimer's disease

1 week 5 days ago
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide and the leading cause of dementia in older adults. The presence of extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) constitutes the two principal neuropathological features of AD. However, current therapies targeting only Aβ or tau remain suboptimal, likely due to intrinsic neuronal and glial dysfunction in affected brain regions. Urolithin A (UroA) is a widely recognized...
Jiawei Xiang

The mitochondria-synapse axis in Alzheimer's disease: Lost coordination in early stages

1 week 5 days ago
Synaptic dysfunction emerges early in Alzheimer's disease, often years before the appearance of clinical symptoms, and is among the most reliable predictors of subsequent cognitive decline. Despite its importance, the cellular events that trigger this early synaptic vulnerability remain poorly defined. Growing evidence points to a critical failure at the interface between neuronal energy metabolism and synaptic signalling, commonly referred to as the mitochondria-synapse axis, suggesting that...
Priyanshu Sharma

The sound of longevity: music and technology for healthy ageing

1 week 5 days ago
A growing body of research is focusing on how music, technology, and neuroscience can converge to promote healthy ageing and counteract pathological decline. In particular, music interventions for older adults have been garnering increasing attention, with numerous reports showing positive effects of music on various health outcomes, including psychological well-being, cognitive function, physiological responses, quality of life, and overall well-being. In this context, the European...
Fiona Ecarnot

Multimodal clocks of human aging

1 week 5 days ago
Human aging is characterized by complex structural and functional decline, but quantifying its heterogeneity and assessing biological age remain challenges. We present the mCAS (multicentric Chinese aging standardized cohort) developed from 2,019 Chinese individuals aged 18-91 years. Integrating high-dimensional clinical, physiological, and molecular-level data, we constructed a three-tiered aging framework: the core capacity clock (CC-clock) to quantify clinical physiological decline, the...
Jiaming Li

Even single-domain decline in physical performance predicts short- and long-term mortality in older adults

1 week 5 days ago
CONCLUSIONS: These results suggest that even decline confined to a single physical performance domain may signal an early transition toward increased vulnerability. Monitoring trajectories of physical performance may therefore help identify older adults at increased mortality risk before more widespread functional deterioration becomes apparent.
Chiara Ceolin

Developmental origins of exceptional health and survival: a four-generation family cohort study

1 week 5 days ago
Descendants of longevity-enriched sibships demonstrate a broad health and survival advantage throughout the life course. However, little is known about manifestations during very early life. Here we show a pattern of lower risk of adverse early-life outcomes in third-generation grandchildren (N = 5637) of Danish longevity-enriched sibships compared to the general population, including infant mortality (Hazard Ratio = 0.53, 95% CI [0.36, 0.77]) and a range of neonatal health indicators. These...
Matthew Thomas Keys

sc-ChromAging: A Single-Cell Chromatin Accessibility-based Clock Decodes Cell-Type-Specific Epigenetic Aging Trajectories

1 week 5 days ago
sc-ChromAging, a chromatin accessibility-based aging clock, was developed using single-cell ATAC-seq from 401 Chinese individuals. It identified CD4⁺ naive T cells as the most accurate predictors of age. This clock linked immune aging with pathways in inflammation, infection, and tumor susceptibility, and connecting chromatin changes to plasma metabolites like triacylglycerols.
Xindi Wei

Scientists found the “holy grail” gene that could one day help humans regrow limbs

1 week 6 days ago
Scientists studying axolotls, zebrafish, and mice have uncovered a shared set of genes that may one day help humans regrow lost limbs. By identifying powerful “SP genes” involved in regeneration, researchers discovered that disabling these genes stopped proper bone regrowth in salamanders and mice. They then used a gene therapy inspired by zebrafish biology to partially restore regeneration in mice, marking a major step toward future treatments that could replace damaged limbs with living tissue instead of prosthetics.

New obesity discovery rewrites decades of fat science

1 week 6 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

1 week 6 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

1 week 6 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

1 week 6 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

1 week 6 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

1 week 6 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

1 week 6 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

1 week 6 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

1 week 6 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