Aging

Biomarkers of aging, particularly DNA methylation-based clocks, have shown promise as tools to assess whether interventions may impact the rate of biological aging. Among possible interventions physical exercise has shown protective effects against many age-associated diseases, while time-restricted feeding (TRF), has shown metabolic benefits in preclinical models. The combined effect of exercise and TRF on aging biomarkers remains largely unexplored. In this 52-week four-armed, randomized, cont...

BackgroundIsocitrate dehydrogenase wildtype (IDHwt) histologic grade 2 adult diffuse gliomas represent a highly heterogeneous entity, and the effects of postoperative adjuvant temozolomide (TMZ) therapy, as well as the predictive value of chemotherapy-related biomarker O6-methylguanine-DNA methyltransferase promoter (MGMT-p) methylation, remain to be further investigated. MethodsA Discovery dataset, comprising 108 IDHwt histologic grade 2 gliomas obtained from three public resources, was constr...

Cellular senescence increases in frequency with age and is implicated in age-related pathologies, and identifying circulating biomarkers of senescence holds great diagnostic potential. Circulating senescence signatures are predictive of many age-related traits and diseases, though cell type-specific senescence signatures have not been comprehensively explored. In this study, senescence signatures from the Senescence Catalog (SenCat), including 14 human cell types such as peripheral blood mononuc...

Societies are aging rapidly in parallel with the increasingly earlier onset of serious diseases in younger populations. These and other factors are creating a substantial disparity between healthspan, the period of life where an individual is free from serious chronic disease or disability, and lifespan -- expanding the morbidity span. Extending healthspan has thus become a major priority. To pursue an integrated strategy toward healthspan support, we launched DELTA, a prospective, open-label, i...

DNA repair capacity (DRC), particularly at the pathway level, varies among individuals. While previous studies explored DRC in relation to environmental exposures and cancer risk, few measured DRC in patient-focused cohorts and were focused on one or two repair pathways only. We comprehensively profiled DRC for all the major repair pathways and DNA lesions in 100 lung cancer patients undergoing radiotherapy (RT) using advanced Fluorescence Multiplex based Host Cell Reactivation assays in blood c...

BackgroundIntrinsic capacity (IC) is a key marker of healthy ageing, which captures an individuals physical and mental capacities, measured across five domains: cognitive, locomotor, psychological, vitality, and sensory. Although genetic factors are known to influence both general IC and its individual domains, existing IC indices have been developed primarily using phenotypic data, without accounting for the underlying biological architecture across domains. In this study, we developed a multi-...

BackgroundBody composition strongly influences clinical outcomes in older adults, yet body mass index (BMI) lacks discriminatory power, and standard tools such as bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry are not routinely accessible. Deep learning enables scalable, opportunistic assessment of body composition from chest radiographs (CXRs), one of the most widely available imaging modalities. Methods and FindingsUsing the Inception-V3 architecture, we developed a ...

Regular physical activity delays biological ageing, yet how transient exercise-induced molecular responses are translated into stable ageing signatures in humans remains unclear. Here, we introduce the first in silico perturbation framework for human exercise biology that integrates genetically anchored gene prioritisation, graph-based network modelling, and human experimental validation. Genes causally associated with habitual vigorous physical activity (VPA) were prioritised using Mendelian ra...

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high mortality rates, often exhibiting resistance to conventional treatments such as radiotherapy (RT) or a combination of chemotherapy and radiotherapy (CRT). The nerve growth factor receptor (NGFR, also known as p75NTR or CD271) is a well-established cancer stem cell marker in melanoma, where it has been linked to resistance to multiple therapies. In HNSCC, NGFR has been reported as a poor prognostic marker, with it...

Background and AimsAvoidance of symptom-related situations is common in chronic gastrointestinal (GI) conditions, contributing to greater symptom severity, psychological distress, and reduced quality of life. However, no validated measure exists to comprehensively assess GI-specific avoidance. We developed and validated the GI-specific Avoidance Scale (GIAS), a self-report instrument measuring behavioral and cognitive avoidance specific to GI symptoms. MethodsFollowing literature review and mul...

Adaptation to physiological stress is fundamental to health but varies widely among individuals. In humans, this heterogeneity is evident in markedly different gains in fitness in response to identical exercise training. The molecular determinants of this variable "trainability" remain poorly understood. Here we identify insulin-like growth factor binding protein-7 (IGFBP7), a senescence-associated secreted protein, as a circulating constraint on exercise adaptation. Plasma proteomics in older a...

BackgroundMenopausal obesity is a type of obesity in women during menopause where the decline of ovarian function and the decrease of estrogen levels lead to an imbalance between energy intake and consumption in the body, resulting in fat accumulation and weight gain. Moxibustion, as a green therapy of non-interventional external treatment that prevents and treats diseases through thermal stimulation of relevant acupoints, has been widely used in clinical practice because of its simplicity, conv...

Aging is accompanied by a decline in physiological function and increased vulnerability to disease, with mitochondrial dysfunction and epigenetic alterations recognized as key hallmarks. Nicotinamide riboside (NR), a vitamin B3 precursor to NAD, and high-intensity interval training (HIIT) have both been proposed to ameliorate aging-related mitochondrial decline, but their effects on skeletal muscle epigenetic aging are not fully elucidated. Here, we assessed the impact of 5-month NR supplementat...

BackgroundPerianal Crohns disease (PCD) represents one of the most severe and refractory forms of pediatric inflammatory bowel disease (IBD). Constipation and colonic redundancy, particularly type 1 dolichocolon (T1-DC), may increase distal rectosigmoid pressure, and exacerbate perianal pathology. We hypothesized that T1-DC is more common in children with PCD than in those with uncomplicated ileocolonic Crohns disease (CD) or non-IBD controls. MethodsWe retrospectively analyzed 20 consecutive p...

IntroductionObesity and related cardiometabolic comorbidities, including hypertension, dyslipidemia, diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD), and atherosclerotic cardiovascular disease (ASCVD), are increasingly prevalent among individuals with inflammatory bowel disease (IBD). These conditions influence disease activity, therapeutic response, surgical outcomes, and overall quality of life, yet evidence remains fragmented. The Modulate Obesity and relateD metabo...

BackgroundScalable, non-invasive markers for cognitive-decline risk are limited. Olfactory dysfunction is predictive, and oral dysbiosis is mechanistically linked to neurocognitive pathways. Hence, we tested whether pairing smell and global cognition with salivary microbiome profiling yields a targeted, clinically useful signal. MethodsWe enrolled 113 Memory Center attendees and community controls. Same-day MMSE, UPSIT, and saliva were obtained for 16S rRNA gene sequencing and cytokine measurem...

BackgroundHFE p.C282Y (c.845G>A; rs1800562) is a common missense mutation in persons of European ancestry, but we found no comprehensive tabulation of p.C282Y allele frequencies in Iberia. MethodsWe performed computerized and manual searches to identify evaluable reports of p.C282Y alleles in population/control cohorts [≥]50 subjects in Iberia. We tabulated numbers of subjects, nominal geographic sites of cohort recruitment, cohort characteristics, corresponding latitudes and longitudes, and...

BackgroundPeak educational attainment is linked to early life general cognitive abilities, mid-life socioeconomic status, and late-life dementia risks. Yet, it is difficult to study its mechanisms acting across decades of life given diverse paths towards peak attainment and lifelong learning opportunities. MethodsWe analyzed profiles of peak educational attainment, adult learning (formal, job-related, non-formal, informal), and their relationships to novel plasma proteomic markers of age in a r...

Aging is accompanied by molecular changes across multiple biological systems that contribute to functional decline and increased disease risk, but the underlying mechanisms and inter-individual variation remain poorly understood. We investigated whether multi-omics integration can reveal coordinated molecular processes associated with accelerated PhenoAge, a clinical biomarker-based estimate of biological aging. Using UK Biobank data from [~]20,000 participants, we integrated plasma proteomics a...

Background and ObjectiveThe dysbiosis of human gut microbiome has been increasingly seen to have a relation in the development of autoimmune diseases, with specific microbial signatures having causative association with specific conditions. Inflammatory bowel disease (IBD) is one such autoimmune ailment. This paper proposes a predictive tool that can identify the IBD status of an individual based on the composition of the gut microbiome using machine learning and AI agents driven techniques. The...