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Age acceleration, or the difference between biological and chronological age, is a research area of growing interest, particularly in the field of age-related and neurodegenerative disorders, including Alzheimer's disease (AD). First-generation epigenetic clocks that predict chronological age utilising DNA methylation data were the first to derive estimates of age acceleration, which have been associated with several age-related conditions. More recently, second-generation epigenetic clocks that...

Alzheimer's disease (AD) involves early disruptions in brain connectivity, yet how AD risk markers relate to resting-state dynamic functional connectivity (rs-dFC) remains unclear. We examined associations of AD pathology, genetic risk, and blood-based biomarkers (BBMs) of neurodegeneration with local and distant rs-dFC in cognitively normal older adults and explored links with cognitive performance. Baseline data from 86 cognitively normal older adults in the AGUEDA trial (NCT05186090) were...

Telomere length (TL) has been proposed as a marker of appendicular lean mass (ALM) decline; however, longitudinal evidence remains limited. We aimed to investigate the longitudinal association between TL and 6-year trajectories of ALM. This longitudinal study included 185 older adults aged 55-75 years with overweight or obesity and metabolic syndrome at baseline. Baseline TL was assessed using a monochrome multiplex real-time quantitative PCR. ALM from the four limbs was obtained at baseline,...

Immune checkpoint blockade (ICB) shows limited efficacy in pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that ICB-induced IFN-γ signaling upregulates H2-T23 on pancreatic tumor cells, which interacts with NKG2A on NK cells to induce NK cell senescence through activation of p38 MAPK and STAT1/3 pathways. This impairs NK cell cytotoxicity and restricts antitumor immunity. Dual blockade of PD-1 and NKG2A effectively prevents NK cell senescence, restores NK cell function, and...

CONCLUSION: SSDH that shape dementia risk and brain resilience, many modifiable at the community and policy levels, remain unevenly collected in Canadian aging and dementia cohorts. Strengthening and harmonizing SSDH measurement is a critical step toward equitable dementia prevention and reducing health disparities.

Spin glasses are magnetic materials exhibiting numerous magnetization patterns, that randomly vary both in real space and in time. To date, it is still not well understood what the nature of these spatiotemporal dynamics is, namely if they are completely random or if there are relevant and correlated length and time scales. Here, we demonstrate dynamic heterogeneity in the aging dynamics of elemental neodymium. We used spin-polarized scanning tunneling microscopy in combination with atomistic...

Posttraumatic stress disorder (PTSD) is associated with increased risk of chronic disease and premature aging, yet underlying molecular mechanisms remain unclear. We performed plasma proteomics (SomaScan; 9404 proteins) and targeted metabolomics (145 metabolites) in 393 World Trade Center responders (232 with PTSD, 161 trauma-exposed controls). A total of 114 proteins and seven metabolites were differentially expressed in PTSD. Top proteins included NCAN, BCAN, NCAM1, and GDF15. Top metabolites...

Anelloviruses dominate the human plasma virome, yet their lifespan dynamics and relationships with the immune system are unclear. We integrated metagenomics with cytokines, HERV-K, and CMV profiling across 405 individuals (0-100 years) and found that prevalence, abundance, and diversity varied non-linearly with age and by sex. Alphatorqueviruses accumulated progressively with age, while betatorqueviruses and gammatorqueviruses displayed biphasic, female-specific patterns. Alphatorquevirus...

Glial cells shape brain development and aging, yet whether distinct glial lineages undergo coordinated lifespan transitions remains unclear. Although microglial aging states and oligodendrocyte vulnerability in neurodegeneration are well described, it remains unclear whether these programs evolve independently or in a temporally related manner. Here, we analyzed Mouse Cell Atlas single-cell RNA-seq data spanning embryogenesis to 24 months. Microglia and oligodendrocytes were the most...

CONCLUSION: This study demonstrated that Seismofit show a moderate-to-strong association with CPET measurements in older adults. Seismofit, however, systematically overestimated V̇O₂-peak. For Seismofit to be integrated into large-scale cohort studies and experimental research, the methodology used for older adults needs further development.

Eating five servings of fruits and vegetables may not be enough if you're missing foods rich in flavanols, a group of compounds linked to better heart health. Researchers found that choices like blackberries, plums, apples, broad beans, cherries, and green tea can dramatically increase flavanol intake.

A newly identified molecule called OLE helped restore the brain’s immune cells to a more protective state in Alzheimer’s models. The treatment reduced toxic plaque buildup and improved memory, raising hopes for a new therapeutic approach.

After tumultuous Fable 5 takedown, scientists fear AI safety rules could reshape open research

Mitogen-activated protein kinase (MAPK) signaling is increasingly recognized as a central regulator in the pathogenesis of Parkinson's disease (PD). PD is a chronic neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), driven by a complex interplay of mitochondrial dysfunction, oxidative stress, and neuroinflammation. While basal MAPK activity is essential for neuroprotection and neuronal growth, its overactivation,...

Alzheimer's disease (AD) is characterized by a prolonged asymptomatic phase before cognitive decline emerges, yet the mechanisms driving symptom onset remain unclear. Here, we hypothesized that the transition from asymptomatic to symptomatic disease is linked to dysfunction of brain-immune communication. Retrograde neuronal tracing in the 5xFAD mouse model of amyloidosis reveals reduced brain-spleen connectivity at advanced disease stages. To probe the functional role of the brain-spleen axis in...

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition. Studies of postmortem ASD brain tissue have revealed convergent molecular changes across the cortex. Whether these features are reflected in cell-type-specific epigenetic signatures is unknown. Here, we present a single-cell analysis of DNA methylation (DNAm) coupled with transcriptomics in ASD. Using snmCT-seq, we profiled DNAm and transcript levels from over 60,000 nuclei derived from the prefrontal cortex of 49...

Whether aging arises primarily from the progressive accumulation of molecular damage (error-based theories) or from regulated, development-related processes (programmatic theories) has been debated for more than a century. This question is central to aging research and shapes our conceptual understanding of aging. Although the existence of a dedicated aging program and the evolutionary advantage of aging remains controversial, the possibility that aging confers adaptive benefits at the species...

Cardiac aging is a fundamental contributor to heart failure, arrhythmias, impaired stress tolerance, and reduced cardiovascular resilience in the elderly. While intrinsic myocardial aging has been widely examined, the systemic mechanisms driving age-related cardiac decline are not fully understood. Circulating extracellular vesicles (EVs) have emerged as key mediators of intercellular and inter-organ communication, transferring proteins, lipids, and nucleic acids that modify the phenotypes of...

CONCLUSIONS: Black older adults without caregivers had the worst observed EOL care quality. Caregiver presence was associated with narrower but persistent racial differences, suggesting structural factors that may attenuate the benefits of caregiving for Black older adults. Policy interventions designed to provide culturally responsive support to minority caregivers may help reduce racial disparities in EOL care quality.

NAT10 is the sole eukaryotic acetyltransferase that catalyzes N4-acetylcytidine (ac⁴C) modification of RNA. While dysregulation of NAT10 is associated with cancer and premature aging syndromes, the requirement for its acetyltransferase activity and how NAT10 coordinates catalysis and RNA binding remain poorly understood. Here, we report single particle cryo-electron microscopy structures of eukaryotic (Chaetomium thermophilum) NAT10 in complex with a designer cytidine-CoA cofactor-based ligand...