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Methionine Restriction Extends Yeast Lifespan by Activating Non-Nitrogen-Starvation-Induced Autophagy Through Limiting Methylation of Protein Phosphatase 2A
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...
The immunoproteome and multimorbidity: A Mendelian randomization study
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,...
Transcranial ultrasound stimulation of motor networks in Parkinson's disease informed by local field potential dynamics
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...
Treating the immune system to repair the brain
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.
Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments
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...
Global evaluation of the impact of nursing interventions on rehabilitation in older patients following fracture
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.
Intrinsic capacity and the risk of adverse health outcomes in older adults: a population-based study
CONCLUSIONS: The total IC score and components of each domain were associated with the risk of falls and functional decline after 5 years.
Mixed methods implementation evaluation of community-based intergenerational program to improve the quality of life of the elderly in rural Maharashtra
CONCLUSION: Community based intergenerational project offer a promising approach to address social isolation and promote well-being in elderly individuals while also enhancing intergenerational connections and community resilience.
FGF21 rejuvenates aged human adipose-derived mesenchymal stem cells via enhancement of TFE3-mediated autophagy flux
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...
Integrative bibliometric and transcriptomic analyses identify selenium-associated molecular signatures in the aging brain
CONCLUSION: This study identifies SP1 and SEPHS2 as key genes linking selenium to brain aging, providing new insights into the role of selenium in brain aging and suggesting that these genes may represent potential biomarkers or therapeutic targets for brain aging and aging-related brain disorders.