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Methionine Restriction Extends Yeast Lifespan by Activating Non-Nitrogen-Starvation-Induced Autophagy Through Limiting Methylation of Protein Phosphatase 2A

2 weeks 5 days ago
Methionine restriction (MR) extends the lifespan and healthspan of numerous eukaryotic organisms, but the molecular mechanisms at play are unclear. Here we find that the ability of MR to extend the budding yeast chronological and replicative lifespans is the consequence of reduced methionine conversion to the methyl donor S-adenosylmethionine (SAM). Mechanistically, the key antiaging event downregulated by MR is the methylation of protein phosphatase 2A (PP2A). In chronological aging cells under...
Kaylah Birmingham

The immunoproteome and multimorbidity: A Mendelian randomization study

2 weeks 5 days ago
Multimorbidity presents challenges for research and health care. We investigated how immune-proteins influence multiple diseases to identify shared mechanisms and therapeutic opportunities. Using eight large plasma proteome GWAS, we identified cis-acting variants for 151 immune-proteins and applied cis-Mendelian randomization to assess associations with 64 diseases and biomarkers. Protein-disease communities were derived using a knowledge graph integrating multiplicity-corrected associations,...
Nikita Hukerikar

Transcranial ultrasound stimulation of motor networks in Parkinson's disease informed by local field potential dynamics

2 weeks 5 days ago
Transcranial ultrasound stimulation (TUS) is a promising noninvasive technique for modulating deep brain targets and circuits with high spatial precision. For its successful clinical translation, confirmation of target engagement, together with a deeper understanding of the effects of TUS, is essential. To advance these goals, we obtained direct measures of neural activity using electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) during TUS of deep and...
Can Sarica

Treating the immune system to repair the brain

2 weeks 5 days ago
Non-neuronal brain cells and systemic immunity play a central role in Alzheimer's disease (AD) and other brain disorders. The immune system, initially protective, becomes dysfunctional as the disease progresses. Here, we discuss next-generation therapeutic approaches aimed at treating the immune system rather than the brain to combat AD and other neurodegenerative diseases.
Michal Schwartz

Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments

2 weeks 5 days ago
The assembly of tau into amyloid filaments is associated with more than 20 neurodegenerative diseases, collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of brain-derived tau filaments revealed that specific structures define different diseases, triggering a quest for the development of experimental model systems that replicate the structures of disease. Here, we describe 12 phosphomimetic serine/threonine-to-aspartate mutations in tau, which we term PAD12, that...
Sofia Lövestam

Global evaluation of the impact of nursing interventions on rehabilitation in older patients following fracture

2 weeks 5 days ago
CONCLUSION: It was found that nursing interventions in the observational group, compared to the control group, significantly improved satisfaction rates and alleviate complication rates. These findings suggest that various nursing intervention programs can effectively enhance rehabilitation outcomes in older patients following fractures.
Qiong Xiong

FGF21 rejuvenates aged human adipose-derived mesenchymal stem cells via enhancement of TFE3-mediated autophagy flux

2 weeks 5 days ago
Intracerebral hemorrhage (ICH) is a neurological disorder characterized by a high mortality rate for which there is currently no definitive cure. Research has demonstrated that adipose-derived mesenchymal stem cells (ASCs) exhibit considerable potential in treating ICH. However, the advanced age of ICH patients and the necessary cell expansion before transplantation therapy could result in the senescence of ASCs, thereby compromising their viability and therapeutic efficacy. This study aims to...
Bei Song