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Nanomedicine Guiding Mitochondrial Function in the Treatment of Cardiovascular Diseases: Mechanisms, Latest Developments, and Clinical Translation

1 week 6 days ago
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide, and ageing is their strongest biological risk factor. In the ageing cardiovascular system, mitochondrial dysfunction is not only a central driver of disease progression but also a key feature of cardiovascular ageing, linking oxidative stress, calcium dysregulation, bioenergetic failure, impaired mitochondrial dynamics, defective mitophagy, and chronic inflammation to myocardial and vascular decline. In...
Fuyun Jia

Age-associated regulation of chondrocyte hypertrophy in osteoarthritis: Mechanisms, therapeutic implications, and cartilage fate reprogramming

1 week 6 days ago
Osteoarthritis (OA) is a prevalent age-associated joint disease marked by progressive cartilage loss, subchondral bone remodeling, osteophyte formation, and low-grade inflammation. In OA, articular chondrocytes shift from a stable extracellular matrix (ECM)-maintaining state toward a hypertrophy-like program with increased collagen type X alpha 1 chain (COL10A1), runt-related transcription factor 2 (RUNX2), and matrix metalloproteinase 13 (MMP-13), promoting ECM degradation, calcification, and...
Jong Seong Ha

Unlocking the Gut-Brain-Heart Axis: Mechanistic Insights and Therapeutic Avenues for Sleep and Cardiovascular Comorbidity

1 week 6 days ago
Sleep disorders and cardiovascular diseases are pressing global health concerns, whose prevalence and comorbidity significantly increase with age. The mechanistic underpinnings of this bidirectional relationship remain elusive. This review posits the Gut-Brain-Heart Axis (GBHA) as a critical integrative network bridging this clinical gap, particularly in the context of ageing. We synthesize compelling evidence that sleep disturbances induce gut dysbiosis, compromise intestinal barrier...
Xinge Tang

Chemical anchoring of immunotherapeutic drugs within senescent tumor cells overcomes senescence-driven immunotherapy resistance

1 week 6 days ago
Multidrug resistance (MDR) compromises cancer treatment efficacy and leads to therapeutic failure. Therapy-induced senescence further complicates MDR through senescence-enhanced drug efflux and senescence-associated secretory phenotypes (SASPs), remaining a huge challenge. Here, we develop a self-generative senescence-associated β-galactosidase (SA-β-gal)-initiated chemical anchoring of lysosomal protein approach to counteract drug efflux and reprogram SASPs. A senescence-tumor-targeted...
Wenlong Huang

High-Throughput Screening for Ageing and Age-Related Disease Drug Discovery: Advances and Challenges

1 week 6 days ago
Ageing is the primary risk factor for many chronic, degenerative, and life-threatening disorders, yet the translational pipeline for geroprotective interventions remains comparatively sparse. Short‑lived, experimentally tractable models with conserved ageing pathways, particularly Caenorhabditis elegans, Drosophila melanogaster, and the African turquoise killifish (Nothobranchius furzeri), have expanded discovery beyond traditionally mammalian-centric pipelines. By leveraging advances in...
Xingkun Ji

The impact of ageing on faecal short chain fatty acids levels in apparently healthy adults: A systematic review and meta-analysis

1 week 6 days ago
Ageing is accompanied by physiological and lifestyle changes that may influence gut microbial metabolism. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, are microbial metabolites derived from dietary fibre fermentation and play important roles in host metabolic and immune function. This systematic review and meta-analysis examined age-related differences in faecal SCFA concentrations among apparently healthy adults. Following PRISMA guidelines, searches across five...
Saleha Alqarni

ProtFI, an efficient frailty-trained proteomics-based biomarker of aging, robustly predicts age-related decline

1 week 6 days ago
Many molecular aging biomarkers have been developed to capture heterogeneity in individual aging rates. Yet, systematic comparison of the modeling choices underlying these biomarkers has been limited. In this study, we trained aging biomarkers on the Rockwood frailty index (FI) and all-cause mortality using UK Biobank Olink proteomics and metabolomics (¹H-NMR) data (n = 40,696). We systematically established the impact of model choice, target outcome, and molecular data source on several...
Swier Garst

Activation of neurogenesis improves amyloid-beta pathology and cognitive function through AMP kinase signaling in Alzheimer's disease model mice

2 weeks ago
Adult hippocampal neurogenesis declines with aging and in neurological disorders, leading to cognitive impairment. We previously showed that inducing Plagl2 and antagonizing Dyrk1a (iPaD) rejuvenates aged neural stem cells (NSCs), enhancing neurogenesis and cognition in aged mice. Here, we found that NSC-specific iPaD treatment activates neurogenesis, reduces amyloid-β deposition, and improves cognition in Alzheimer's disease model mice. Transcriptomic analysis revealed widespread changes in...
Masahiro Fukui

Experimental and computational methods for allelic imbalance analysis from single-nucleus RNA-seq data

2 weeks ago
Combining allele-specific expression (ASE) analysis with single-cell RNA-seq can elucidate how genomic variation affects RNA expression at the single-cell level. We explore how experimental and computational choices impact the power of ASE-based methods and develop a suite of single-cell ASE computational tools. With single-nucleus RNA-Seq, we extract more ASE information from reads in intronic than exonic regions. We show how read length can increase power and that hybrid selection improves...
Sean K Simmons

Grip strength modifies the association between blood-based alzheimer's biomarkers and cognitive function

2 weeks ago
Blood-based biomarkers are increasingly used to characterize Alzheimer's disease (AD)-related pathology, yet substantial heterogeneity exists in how biomarker burden relates to cognitive performance. Grip strength, a marker of frailty and functional reserve, may modify this relationship. We conducted a cross-sectional analysis of 348 participants from the Aging Adult Brain Connectome (AABC) study. Global cognition was assessed using the Preclinical Alzheimer Cognitive Composite (PACC). Plasma...
Semere Bekena

Genome-wide association study and pathway analysis of healthy aging in Super Seniors

2 weeks ago
Healthy aging is a complex process influenced by genetic, environmental, and lifestyle factors. Although prior genetic studies have identified loci associated with longevity, replication has often been limited by strong non-genetic influences. To investigate the genetic contributors to healthy aging, we performed a genome-wide association study (GWAS) and pathway analyses in 597 Super Seniors-individuals aged ≥ 85 years with no history of cancer, cardiovascular disease, diabetes, dementia, or...
Rawnak Hoque