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Targeting Ubiquitinated Protein Aggregates in Neurodegenerative Diseases: current Status and Future Directions

13 hours 7 minutes ago
Various cellular stressors inhibit translation initiation and promote ribosome disassembly, thereby transiently inducing stress granules (SGs), dynamic ribonucleoprotein condensates that contain mRNAs and RNA-binding proteins. Although SG assembly is usually reversible, dysregulated SG dynamics can trigger the formation of persistent ubiquitin-positive protein inclusions. There is increasing evidence that this conversion of SGs into insoluble aggregates represents a central pathogenic mechanism...
Masahiko Takahashi

Methylation clocks fail to generalize across genetically admixed individuals

13 hours 7 minutes ago
Epigenetic aging clocks based on DNA methylation patterns across the genome have emerged as a potential biomarker for risk of age-related diseases, like Alzheimer's disease (AD), and environmental and social stressors. However, methylation clocks have not been comprehensively validated in genetically diverse individuals. Here, we evaluate a set of first-, second-, and third-generation methylation clocks in 621 AD patients and matched controls from African American, Hispanic, and White cohorts....
Sebastián Cruz-Gonzalez

Proteome dynamics reveal Leiomodin 1 as a key regulator of myogenic differentiation

13 hours 7 minutes ago
During myogenic differentiation, the cellular architecture and proteome of muscle stem cells and myoblasts undergo extensive remodeling. These processes are partially understood and display alterations in disease and aging, resulting in impaired regeneration. Here, we used mass spectrometry to quantify the temporal dynamics of over 6000 proteins during myogenic differentiation. We identified the actin nucleator leiomodin 1 (LMOD1) among a restricted subset of cytoskeletal proteins increasing in...
Ellen Späth

Association of neurofilament light chain, CXCL9, IL-6, and TNFRSF11B with intrinsic capacity in community-dwelling older adults

13 hours 7 minutes ago
Intrinsic capacity (IC) reflects multidomain functional reserve and a measurable phenotype of healthy ageing, but its biological correlates remain incompletely understood. We examined associations of neurofilament light chain (NfL), CXCL9 and inflammatory biomarkers with IC in community-dwelling older adults. We conducted a cross-sectional analysis within the Screening and Prevention of Intrinsic Capacity Decline in Elders (SPICE) programme. IC was derived from locomotion (SPPB), cognition...
Reshma Aziz Merchant

Multimodal MRI prediction of cognitive functioning across the lifespan: separating between-person differences from within-person changes

13 hours 7 minutes ago
Brain MRI shows promise for predicting cognitive functioning, but its utility depends on its capacity to capture stable between-person differences (e.g., patient stratification), longitudinal within-person changes (e.g., prognosis, treatment monitoring), or both. Using longitudinal data from 450 adults (aged 21-90; up to three waves, five years apart) in the Dallas Lifespan Brain Study, we benchmarked five modalities, task fMRI, functional connectivity (FC), structural MRI (sMRI),...
Kseniia Konopkina

In-situ glial cell-surface proteomics identifies pro-longevity factors in Drosophila

13 hours 7 minutes ago
Much focus has shifted towards understanding how glial dysfunction contributes to age-related neurodegeneration due to the critical roles glial cells play in maintaining brain health. Cell-cell interactions, which are largely mediated by cell-surface proteins, control many critical aspects of development and physiology; as such, dysregulation of glial cell-surface proteins is hypothesized to play an important role in age-related neurodegeneration. However, it remains technically difficult to...
Madeline P Marques

Methylation clocks fail to generalize across genetically admixed individuals

13 hours 7 minutes ago
Epigenetic aging clocks based on DNA methylation patterns across the genome have emerged as a potential biomarker for risk of age-related diseases, like Alzheimer's disease (AD), and environmental and social stressors. However, methylation clocks have not been comprehensively validated in genetically diverse individuals. Here, we evaluate a set of first-, second-, and third-generation methylation clocks in 621 AD patients and matched controls from African American, Hispanic, and White cohorts....
Sebastián Cruz-Gonzalez

Pericyte K<sub>ATP</sub> channel hyperactivity redistributes cortical blood flow in a CADASIL mouse model

13 hours 7 minutes ago
Cerebral hemodynamic dysfunction is a key driver of unhealthy brain aging. Impaired microcirculatory reactivity leads to uneven perfusion, rendering deeper brain regions more vulnerable and thereby contributing to cognitive decline. Yet how capillaries contribute to these deficits remains poorly defined. Here we combined spatial transcriptomics with in vivo two-photon and three-photon imaging to measure layer-specific cerebral blood flow in control and small vessel disease model mice (CADASIL...
Danielle A Jeffrey

Memory training through Chinese classics recitation for individuals with subjective cognitive decline: study protocol for a pilot study

13 hours 7 minutes ago
BACKGROUND: Subjective cognitive decline (SCD) is a preclinical condition associated with an increased risk of dementia and Alzheimer's disease, with no consensus regarding effective therapeutic interventions to date. As the global burden of aging-related neurodegenerative diseases continues to rise, early intervention has become increasingly critical. Cognitive training has been proposed as a promising behavioral intervention; however, few studies have integrated multimodal assessments to...
Tz-Syuan Su

<em>Caenorhabditis elegans</em> in neuroscience: from neural communication to neurodegenerative disease modeling

13 hours 7 minutes ago
Consistent with humans and other metazoans, the nematode Caenorhabditis elegans (C. elegans) undergoes progressive structural and functional decline during aging. Possessing highly conserved genetic pathways that share extensive homology with human genes, and characterized by a streamlined, fully mapped connectome, C. elegans has emerged as a robust model for dissecting the mechanisms underlying neuronal aging and degeneration. In this review, we summarize the intrinsic advantages of C. elegans...
Ziheng Pan

Targeting the NO-cGMP axis in age-related vascular dysfunction: a systematic review and meta-analysis of preclinical animal studies

13 hours 7 minutes ago
Vascular dysfunction in aging is driven by multiple interconnected hallmarks of aging, including DNA damage, oxidative stress, chronic inflammation, mitochondrial dysfunction, and cellular senescence and features by endothelial impairment, inflammation, and reduced nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling. Targeting this pathway may offer therapeutic benefit beyond traditional atherosclerosis-focused treatments. A systematic review and meta-analysis were conducted...
Soroush Mohammadi Jouabadi