Aging & Longevity

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...

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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...

Despite the well-known role as degradative organelles, lysosomes have been identified as a central signaling hub in maintaining cellular homeostasis. Lysosomal dysfunction is a well-established driver of cellular senescence and age-related pathologies. However, the precise molecular mechanisms through which lysosomes actively regulate aging remain unclear. Excitingly, latest studies show that lysosomes are not merely passive in aging but may actively govern longevity. In this review we summarize...

Promoting brain health is vital for well-being and reducing healthcare burdens. Brain health as measured with the Brain Age Gap (BAG) - the difference between chronological and predicted brain age- relates to many factors. However, a holistic view, integrating the range of factors an individual brain is exposed to, is missing for understanding how the exposome shapes brain health. After computing BAG as an indicator of grey matter (GM) health, we predicted it using machine learning based on 261...

Lab-scale wastewater treatment studies, including urine recovery, often rely on oversimplified synthetic wastewater, thereby compromising the reliability of results and data. Here, we systematically evaluate how using full-component versus simplified synthetic urine formulations affects the performance and engineering-economic assessment of bipolar membrane electrodialysis. Our findings reveal that simplification fundamentally alters fouling mechanisms. While urea alone causes significant damage...

Pleural Mesothelioma (PM) is an aggressive neoplasm of the lung pleura with poor survival rates, highlighting the urgent need for novel therapeutic options. The CDK4/6 inhibitors abemaciclib and palbociclib have demonstrated promising results in patient-derived xenograft models of PM. In this study, we observed that palbociclib reduced proliferation, leading to increased cell size, enhanced SA-β-galactosidase activity, and elevated secretion of IL-6 and IL-8 (SASP), all of which are hallmarks of...

Abnormal cell fate transition determines cell instability, which can contribute to disease development. In chronic kidney disease, many renal tubular cells exhibit senescent phenotypes. The fundamental mechanisms of this fate transition remain undetermined. Here we discover that WNT10B, a ligand of the Wnt family, accelerates CKD progression through tubular senescence and proinflammatory microenvironments. Mechanistically, WNT10B mediates metabolic reprogramming from fatty acid oxidation to...

Immune defenses decline with age, increasing susceptibility to influenza. Vaccination remains the most effective strategy to prevent severe disease and death, but its efficacy is reduced in older adults, particularly against influenza A(H3N2). The mechanisms underlying this age-related decline in vaccine-specific antibody responses remain unclear. We investigated the magnitude and quality of influenza-specific T-cell responses following quadrivalent inactivated influenza vaccination in adults...

CONCLUSIONS: Inclusion of fish in a healthy and balanced diet is associated with better white matter grades on MRI and slower progression of white matter hyperintensities and reduction of vascular-related lesions of the aging brain, suggesting a potential role in preventing neurocognitive deterioration. Heterogeneity across studies underscores the need for additional studies.

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Cellular senescence is defined as an irreversible growth arrest observed when cells are exposed to a variety of stressors, including DNA damage, oxidative stress, or nutrient deprivation. Although senescence is a well-established driver of aging and age-related diseases, it is a highly heterogeneous process with significant variations across organisms, tissues, and cell types. The relatively low abundance of senescent cells in healthy aged tissues poses a major challenge to the longitudinal...

Niemann-Pick disease type C (NPC) is a rare autosomal recessive disorder characterized by progressive neurodegeneration, primarily caused by a functional defect in NPC1 resulting from gene mutations. NPC1, a lysosomal transmembrane protein, acts as a transporter of cholesterol from the lysosome to the endoplasmic reticulum, and its dysfunction results in the intracellular accumulation of unesterified cholesterol. Although microgliosis with accumulated cholesterol has been reported in NPC, the...

Emergency department (ED) length of stay (LOS) is associated with adverse outcomes and increases with age, but the extent to which this reflects differences beyond triage acuity is unclear. Emergency department (ED) length of stay (LOS) is associated with adverse outcomes and increases with age, but the extent to which this reflects differences beyond triage acuity is unclear.We conducted a retrospective cohort study of adult ED visits at a tertiary hospital in Hungary between 2016 and 2023 (n =...