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Author Correction: RNA codon expansion via programmable pseudouridine editing and decoding
Death threats to NIH official spark debate over aggressive campaign to end animal research
White Coat Waste Project files complaint over government employee’s emails claiming it incited harassment against Nicole Kleinstreuer
New method reveals perhaps the most massive black hole yet spotted
Big brute 5 billion light-years from Earth is 36 billion times as massive as the Sun
NIH ponders overhauling HIV budget to capitalize on prevention breakthrough
Scientists warn $1 billion push for “implementation science” spurred by promise of lenacapavir will hurt research on new treatments and vaccines
The role of hemoglobin/red cell distribution width value in predicting early major adverse events after open heart surgery in elderly patients
CONCLUSION: In this study, we showed for the first time in the literature that the HRR value calculated from preoperative blood values is a key predictor for in-hospital MAE. In these patients, the HRR value can be used as a preoperative risk biomarker.
Analysis of variability and epigenetic age prediction across microarray and methylation sequencing technologies
Using 100 technical replicate samples from two adult buccal cohorts, we compared technical methylation variability and signal strength between the Infinium MethylationEPIC v2.0 array and the Twist Human Methylome Panel across 753,648 shared CpGs. Twist methylation sequencing showed skewed methylation distributions and fewer highly correlated CpGs than MethylationEPIC arrays. Variance analysis revealed a skew toward higher signal strength in MethylationEPIC datasets, with a subset of CpGs showing...
Efficacy of progressive resistance training intensities and adequate dietary protein intake for community-dwelling frail older adults (TEAMS study), protocol for a randomised controlled trial
BACKGROUND: Progressive Resistance Training (PRT) and adequate dietary protein are crucial for preventing and managing sarcopenia and frailty in older adults. To date, the optimal intensity of PRT and the added value of dietary protein for enhancing muscle mass, strength, and physical performance in frail older adults remain unclear. This randomised controlled trial aims to determine the efficacy of various PRT intensities and adequate dietary protein intake in improving muscle mass, strength...
Advancements in the investigation of the mechanisms underlying cognitive aging
Cognitive aging, a pivotal domain at the intersection of neuroscience and psychology, exhibits a strong association with neurodegenerative disorders; however, its comprehensive underlying mechanisms remain incompletely elucidated. This review aims to provide a thorough synthesis of recent advancements in the investigation of cognitive aging in the brain, highlighting multidimensional assessment techniques, neurobiological foundations, molecular regulatory pathways, systemic changes,...
Pathogens accelerate features of human aging: A review of molecular mechanisms
Many models of aging assume that processes such as cellular senescence or epigenetic alteration occur under sterile conditions. However, humans sustain infection with viral, bacterial, fungal, and parasite pathogens across the course of a lifetime, many of which are capable of long-term persistence in host tissue and nerves. These pathogens-especially members of the human virome like herpesviruses, as well as intracellular bacteria and parasites-express proteins and metabolites capable of...
A unique subpopulation of wild-type neurons recapitulating familial Alzheimer's disease phenotypes
Mutations in the genes encoding APP, Presenilin-1 (PSEN1), and PSEN2 result in early-onset Alzheimer's disease (AD). Previous studies, using iPSC-derived neurons and/or knock-in mice, elucidated the characteristics of neurons expressing familial AD (fAD) mutations. Here, we employ biochemical and state-of-the-art fluorescence imaging assays and report the discovery of a unique subpopulation of wild-type neurons strikingly recapitulating key phenotypes previously identified in the fAD neurons,...
Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy
Mutations that disrupt the clearance of damaged mitochondria via mitophagy are causative for neurological disorders including Parkinson's. Here, we identify a Mitophagic Stress Response (MitoSR) activated by mitochondrial damage in neurons and operating in parallel to canonical Pink1/Parkin-dependent mitophagy. Increasing levels of mitochondrial stress trigger a graded response that induces the concerted degradation of negative regulators of autophagy including Myotubularin-related phosphatase...
Design of Ig-like binders targeting α-synuclein fibril for mitigating its pathological activities
Parkinson's disease (PD) is characterized by the accumulation and spread of pathological α-synuclein (α-syn) fibrils, which contribute to neuroinflammation and neurodegeneration. Here we show that two immunoglobulin-like (Ig-like) domains derived from α-syn receptors, the D1 domain of lymphocyte-activation gene 3 (L3D1) and the V domain of advanced glycation end-products (vRAGE), effectively block cell surface binding of α-syn fibrils, suppress fibrils-induced neuronal α-syn aggregation, and...
Cardiovascular inflammaging: Mechanisms, consequences, and therapeutic perspectives
Both aging and systemic inflammation are major risk factors for cardiovascular disease. This review summarizes the interrelationship of aging and inflammation-known as inflammaging-and the consequences for cardiovascular health. We discuss mechanisms including epigenetic modification, mitochondrial dysfunction, cellular senescence, and gut dysbiosis, many of which are themselves interrelated. Increasing understanding of inflammaging provides an array of biomarkers, some of which are now...
Pathogens accelerate features of human aging: A review of molecular mechanisms
Many models of aging assume that processes such as cellular senescence or epigenetic alteration occur under sterile conditions. However, humans sustain infection with viral, bacterial, fungal, and parasite pathogens across the course of a lifetime, many of which are capable of long-term persistence in host tissue and nerves. These pathogens-especially members of the human virome like herpesviruses, as well as intracellular bacteria and parasites-express proteins and metabolites capable of...
Group-based trajectory modelling for cognitive changes in middle-aged and older adults: A systematic review
CONCLUSION: A substantial proportion of aging individuals maintain cognitive function over time, which may be supported by protective strategies like cognitive/physical engagement, healthy sleep, social connection, and disease management. The adverse outcomes linked to decline trajectories underscore the need for future research on modifiable factors. Comparing predictors across subgroups provides insights into cognitive resilience and proactive protection. Further exploration of biological...
Daily briefing: Lithium supplements reverse Alzheimer's symptoms in mice
No abstract
Modeling the geometry of circadian synchronization and period across aging
Circadian freerunning periods change across the lifespan, yet most computational models do not reproduce these shifts without assuming additional mechanisms. Although the maturation and later deterioration of the suprachiasmatic nucleus (SCN) shape behavioral and humoral rhythms, the underlying driver of period change is more general. We show that it arises from an inherent property of a positively skewed frequency distribution, which naturally follows from a symmetric Gaussian distribution of...
Supramolecular nanostructure mimics GDNF trophic effects in vitro on human dopaminergic neurons
Peptide-based supramolecular nanostructures offer a versatile platform with substantial promise for clinical translation in regenerative medicine. These systems allow for the incorporation of biologically active sequences and can be engineered to modulate tissue-specific parameters such as stiffness, diffusivity, and biodegradability. We developed here a bioactive supramolecular nanostructure containing a peptide designed based on glial cell-derived neurotrophic factor. These nanostructures form...
Structural analyses define the molecular basis of clusterin chaperone function
Clusterin (apolipoprotein J), a conserved glycoprotein abundant in blood and cerebrospinal fluid, functions as a molecular chaperone and apolipoprotein. Dysregulation of clusterin is linked to late-onset Alzheimer disease. Despite its prominent role in extracellular proteostasis, the mechanism of clusterin function remained unclear. Here, we present crystal structures of human clusterin, revealing a discontinuous three-domain architecture. Structure-based mutational analysis demonstrated that...
Plot twist: TET2 clones save the brain
While clonal hematopoiesis (CH) is associated with protection from Alzheimer's disease (AD), a limited understanding of the mechanisms by which this occurs has been a barrier to therapeutic intervention. In a new study, Matatall et al.¹ discover protective mechanisms by which TET2-mutant, but not DNMT3A-mutant, CH impacts dementia pathology and cognition.