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Circadian clocks regulate a myriad of physiological processes rhythmically throughout the day in most organisms. Our study focuses on a relatively less-studied neuropeptide CCHamide1 (CCHa1), expressed in the Drosophila melanogaster gut and the central circadian clock in the brain. We investigated the role of ccha1 on sleep under altered dietary conditions, as well as its impact on metabolism and fitness in Drosophila. We assayed sleep under ad libitum fed, starved and altered protein diets...

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...

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...

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...

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...

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...

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...

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...

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...

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...

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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...

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...

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...

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Myofibrillar myopathy 6 is a rare, autosomal-dominant neuromuscular disorder caused by an amino acid exchange Pro209Leu in the co-chaperone BAG3, which disrupts muscle protein turnover and causes severe muscle weakness and shortened lifespan. We generated transgenic mice overexpressing the human mutant BAG3^(P209L)-GFP, which rapidly develop skeletal muscle weakness unlike controls expressing BAG3^(WT)-GFP. Here we show that mutant mice exhibit sarcomere breakdown, inflammation, protein...

PINK1 serves as the central regulator of PINK1-PRKN-mediated mitophagy, and its precise regulation is critical for efficient mitochondrial clearance. Although the cleavage of PINK1 and its subsequent degradation via the N-end rule pathway under basal conditions are well understood, how full-length PINK1 stability is regulated following mitochondrial damage has remained elusive. In our recent study, we identified the STUB1-VCP/p97 axis as a mechanism that fine-tunes full-length PINK1 levels...

Unusual radio signals could be long-sought smoking gun of galactic mergers

Glial crosstalk surrounding amyloid-β (Aβ) plaques establishes a self-propagating inflammatory niche fueling Alzheimer's disease (AD), yet the molecular triggers remain incompletely defined. We found that the calcium-dependent enzyme peptidyl-arginine deiminase 2 (PAD2) was selectively upregulated in plaque-associated astrocytes in human AD cortex and multiple APP AD transgenic mouse models. Astrocyte-specific deletion of Padi2 in 5×FAD mice rescued learning and memory, lowered Aβ load,...