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Microbe discovery holds promise for sustainable biotechnology
The 1975 discovery of long-lost letters between Albert Einstein and the astronomer Willem de Sitter
Stop destructive fishing in marine protected areas
Insect biodiversity monitoring must be expanded
Prizes must recognize machine contributions to discovery
Quantum effects in electrical circuits honored with Physics Nobel
Breakthrough paved the way to many of today’s budding quantum computers
Missing wind from Milky Way’s giant black hole finally found
Astronomers may have glimpsed a long-predicted wind of gas blowing out from Sagittarius A*
Well-exercised male mice appear to pass fitness to their male offspring
Surprising epigenetic effect relies on snippets of RNA packaged within sperm
Effect of Origanum majorana tea on oxidative stress biomarkers in Parkinson's disease: a randomized placebo-controlled pilot study
CONCLUSION: Origanum majorana infusion may enhance or regulate antioxidant status and reduce oxidative damage in patients with PD. Further studies are warranted to explore its potential therapeutic benefits.
PARL stabilizes mitochondrial BCL-2 via Nur77-mediated scaffolding as a therapeutic strategy for Parkinson's disease
Parkinson's disease (PD) involves both mitochondrial dysfunction and Lewy body pathology. However molecular links between these features remain unclear. Here, we identify Presenilin-associated rhomboid-like protein (PARL) as a Lewy body component, RARL regulates mitochondrial apoptosis via interacting with orphan nuclear receptor Nur77. Clinical profiling revealed reduced plasma PARL levels in 71 PD patients versus controls (p < 0.001), which correlated with disease severity. In MPP^(+)/MPTP...
The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain
The highly conserved CHCHD2 and CHCHD10 are small mitochondrial proteins residing in the intermembrane space. Recently, mutations in the genes encoding these proteins have been linked to severe disorders, including Parkinson's disease and amyotrophic lateral sclerosis. In cultured cells, a small fraction of CHCHD2 and CHCHD10 oligomerize to form a high molecular weight complex of unknown function. Here, we generated a whole-body Chchd2 knockout mouse to investigate the in vivo role of CHCHD2 and...
Structural polymorphism of α-synuclein fibrils alters the pathway of Hsc70-mediated disaggregation
Pathological aggregation of α-synuclein into amyloid fibrils is a hallmark of synucleinopathies, including Parkinson's disease. Despite this commonality, synucleinopathies display divergent disease phenotypes that have been attributed to disease-specific three-dimensional structures of α-synuclein fibrils, each with unique toxic gain-of-function profiles. The Hsc70 chaperone is remarkable in its ability to disassemble pre-existing amyloid fibrils of different proteins in an ATP and...
Senescent macrophages in tumor: phenotypes, roles, and interventions
The senescence of immune cells, including macrophages, that accompany the initiation and development of tumors has become a novel research hotspot. Recently, studies have reported the molecular characteristics of senescent macrophages (sMACs) in the tumor microenvironment (TME), including cell cycle arrest, senescence-associated secretory phenotype (SASP), and senescence-associated β-galactosidase phenotype (SA-β-gal), and these characteristics not only suggest that sMACs are functionally rich...
Comprehensive characterisation of age-related changes in cell subpopulations and tissue structural properties in secondary lymphoid organs
Population aging is an escalating global phenomenon, wherein age-related alterations in the human immune system exacerbate the susceptibility to diseases including infections and autoimmune disorders. Secondary lymphoid organs (SLOs) are key locations for the execution of immunological responses by mature immune cells; however, age-related changes in SLOs remain relatively understudied. To address this gap, this study employed comprehensive approaches including single-cell RNA sequencing...
Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma
The exposome, an individual's lifelong environmental exposure, profoundly impacts health. Somatic tissues undergo functional decline with age, exhibiting characteristic ageing phenotypes, including hair greying and cancer. However, the specific genotoxins, signals and cellular mechanisms underlying each phenotype remain largely unknown. Here we report that melanocyte stem cells (McSCs) and their niche coordinately determine individual stem cell fate through antagonistic, stress-responsive...
Translating cellular senescence research into clinical practice for metabolic disease
Translational research on cellular senescence has led to numerous early-phase clinical trials targeting senescent cells to treat, prevent or alleviate multiple disorders and diseases, including metabolic diseases and their comorbidities. Cellular senescence is a cell fate that occurs in response to stressors, including metabolic disruptions, and is one of the hallmarks (or pillars) of ageing. In their senescent state, cells cease proliferation and can develop a senescence-associated secretory...
The cutting-edge medical approaches that could transform ageing
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Accelerating activity in the longevity biopharmaceutical sector
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HIF1 activity in photoreceptors drives type 3 neovascularization and retinal atrophy in a new mouse model of age-related macular degeneration
Morphological changes in the ageing eye impede oxygen delivery from the choroid to the outer retina causing tissue hypoxia, which activates a molecular response that adapts the transcriptomic fingerprint of the retina and retinal pigment epithelium (RPE). This response, orchestrated by hypoxia-inducible transcription factors (HIFs), leads to the production of pro-angiogenic factors and plays a critical role in the development and pathogenesis of age-related macular degeneration (AMD). To...
Adipocyte FMO3-derived TMAO induces WAT dysfunction and metabolic disorders by promoting inflammasome activation in ageing
Trimethylamine N-oxide (TMAO) contributes to cardio-metabolic diseases, with hepatic flavin-containing monooxygenase 3 (FMO3) recognized as its primary source. Here we demonstrate that elevated adipocyte FMO3 and its derived TMAO trigger white adipose tissue (WAT) dysfunction and its related metabolic disorders in ageing. In adipocytes, ageing or p53 activation upregulates FMO3 and TMAO levels. Adipocyte-specific ablation of FMO3 attenuates TMAO accumulation in WAT and circulation, leading to...