Aggregator

Revealing the temporal evolution of cerebrospinal fluid (CSF) biomarkers during aging is critical to understanding disease pathogenesis and developing early diagnoses and interventions for Alzheimer's disease (AD). CSF was obtained from 549 cognitively normal subjects between 18 and 93 years of age. 12 AD-related biomarkers were evaluated, including amyloid β (Aβ42, Aβ40, Aβ42/Aβ40 ratio), hyperphosphorylated tau (P-tau), neuronal injury/degeneration (T-tau, NFL, NSE, H-FABP, VILIP-1),...

Revealing the temporal evolution of cerebrospinal fluid (CSF) biomarkers during aging is critical to understanding disease pathogenesis and developing early diagnoses and interventions for Alzheimer's disease (AD). CSF was obtained from 549 cognitively normal subjects between 18 and 93 years of age. 12 AD-related biomarkers were evaluated, including amyloid β (Aβ42, Aβ40, Aβ42/Aβ40 ratio), hyperphosphorylated tau (P-tau), neuronal injury/degeneration (T-tau, NFL, NSE, H-FABP, VILIP-1),...

No abstract

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10^(-7); odds ratio [95% confidence interval] = 10.5 [5.2, 21.3]). We replicate this association in three independent datasets totaling 8,407 cases and 413,432 controls...

Accurate diagnosis of early Parkinson's disease requires platforms suitable for detecting minute amounts of neuronally derived biomarkers in the massive protein excess of easily accessible biofluids such as blood. Here, we describe an on-chip droplet-confined fluorescence reporting assay that identified α-synuclein on the membrane of L1CAM+ extracellular vesicles (EVs) immunocaptured from human serum and corroborate this finding by super-resolution direct stochastic optical reconstruction...

Chronic inflammation and a decline in mitochondrial function are hallmarks of aging. Here, we show that the two mechanisms may be linked. We found that interleukin-6 (IL6) suppresses mitochondrial function in settings where PGC1 (both PGC1α and PGC1β) expression is low. This suppression is mediated by the JAK1/STAT1/3 axis, which activates HIF1α through non-canonical mechanisms involving upregulation of HIF1A and ERRα transcription, and subsequent stabilization of the HIF1A protein by ERRα....

Excessive activation of effector-triggered immunity (ETI) in plants inhibits plant growth and activates cell death. ETI mediated by intracellular Toll/interleukin-1 receptor/resistance protein (TIR) nucleotide-binding, leucine-rich repeat receptors (NLRs) involves two partially redundant signaling nodes in Arabidopsis, ENHANCED DISEASE SUSCEPTIBILITY 1-PHYTOALEXIN DEFICIENT 4-ACTIVATED DISEASE RESISTANCE 1 (EDS1-PAD4-ADR1) and EDS1-SENESCENCE-ASSOCIATED GENE 101-N REQUIREMENT GENE 1...

No abstract

CONCLUSIONS: This study demonstrated that higher levels of certain PUFAs were associated with a reduction in PhenoAge acceleration either individually or in combination, with DHA having the most prominent effect in mixed effects. The SII mediated these relationships, suggesting that PUFAs may slow biological aging by reducing inflammation. These findings highlighted the potential role of PUFAs in mitigating accelerated aging and their implications for aging-related health interventions.

Countries are urged to advance the energy transition in a just, orderly, and equitable manner, yet the appropriate pathway remains unclear. Using a provincial-level, hourly-dispatched power system model of China that incorporates intertemporal decisions on early retirement and carbon capture retrofitting, our study reveals that for coal-rich but gas-poor economies, repositioning coal power from a baseload resource to a flexibility provider can accelerate net-zero transition of the power system...

The internationally sourced metal may have helped a predemocratic tyrant rise to power

In 2020, a case report described autologous transplantation of iPSC-derived dopamine (DA) neurons in a Parkinson's disease (PD) patient.¹ The team now follows up with the pre-clinical safety and efficacy data of autologous iPSC-derived DA neurons, forming the basis for regulatory approval of a phase 1 clinical trial involving 8 patients.².

Sleep loss is often regarded as an early manifestation of neurodegenerative diseases given its common occurrence and link to cognitive dysfunction. However, the precise mechanisms by which sleep disturbances contribute to neurodegeneration are not fully understood, nor is it clear why some individuals are more susceptible to these effects than others. This review addresses critical unanswered questions in the field, including whether sleep disturbances precede or result from neurodegenerative...

No abstract

CONCLUSION: Lower oral microbiome diversity is associated with higher frailty and mortality. The number of teeth partially mediates this link, emphasizing the importance of oral health in mitigating frailty and promoting healthy aging.

Stem cells possess an extraordinary ability for self-renewal and differentiation, making them essential for tissue repair, regeneration, and anti-aging. RNA methylation is crucial in regulating stem cell fate by modulating gene expression. This review synthesizes current research on RNA methylation modifications, such as m⁶A, m⁷G, m⁵C, and m¹A, and their impact on adult stem cell fate. It provides a comprehensive overview of the molecular machinery involved in RNA methylation, emphasizes the...

No abstract

No abstract

Mesenchymal cells and the extracellular matrix (ECM) support epithelium during homeostasis and regeneration. However, the role of the mesenchyme in epithelial conversion into a fetal-like regenerative state after damage is not known. We modeled epithelial regeneration by culturing intestinal epithelium on decellularized small intestinal scaffolds (iECM) and identify asporin (Aspn), an ECM-bound proteoglycan, as a critical mediator of epithelial fetal-like reprogramming. After damage, transient...

CONCLUSIONS: The blunting of sex differences in antibody response observed following the primary series by the 1st booster dose underscores the importance of booster vaccination in this population.