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...

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...

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-...

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...

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...

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...

Diet is an essential factor influencing biological aging, yet few exsiting dietary indices were specifically developed to target biological aging. We developed a data-driven food-based Empirical Dietary Index for Slower Epigenetic Aging (EDISEA) in the US Health and Retirement Study (HRS, n=7,398), which predicted deceleration of GrimAge, an established DNA methylation-based epigenetic clock. Participants in the highest versus lowest EDISEA quintile had 4.65-year deceleration in GrimAge (P value...

The biomarker MetaboHealth represents a novel indicator of overall health in middle age and may potentially be suitable as actionable health check in prevention strategies. MetaboHealth is a blood-based metabolomic composite score that predicts a wide range of age-related conditions and mortality in large European cohorts. Here, we investigated whether MetaboHealth can be personalised and limited to clinically validated metabolomic markers. Next, we assessed whether the updated MetaboHealth scor...

BackgroundEpigenetic clocks based on DNA methylation (DNAm) provide quantitative indicators of biological aging. However, the extent to which diverse lifestyle factors influence DNAm-based aging measures remains unclear, especially in Japanese populations. We aimed to evaluate the associations between 52 lifestyle-related factors and multiple epigenetic aging indicators, including six DNAm ages (Horvath, Hannum, PhenoAge, GrimAge, GrimAge v2, and PCPhenoAge specific to Japanese Population), the ...

BackgroundComprehensive data on the prevalence of Helicobacter pylori infection and its associated risk factors among patients with gastrointestinal symptoms remain limited. Generating this evidence would help inform clinical management and improve antibiotic stewardship. H. pylori infection affects a substantial proportion of the global population, with prevalence varying widely across regions. In Uganda, previous studies have documented the presence of H. pylori infection. However, data specif...

Proactive identification of systemic vulnerability for disease(s) before clinical onset in healthy individuals is an ultimate goal of preventive and precision medicine, yet current tools remain largely disease-specific and fail to quantify latent vulnerability, an integrative measure of underlying health status, for early prevention and risk-stratified intervention. To address this, we developed the Risk Score for Disease Vulnerability (RS4DV) based on 85 accessible biopsychosocial measures, whi...

BackgroundVestibular complaints are common in older adults and are linked to imbalance and falls. Some older adults show impaired vestibular perception despite preserved peripheral-reflex ("vestibular agnosia"). Yet it remains unclear if vestibular agnosia is independently linked to imbalance and falls in otherwise healthy older adults. We therefore investigated the prevalence of vestibular agnosia in community-dwelling older adults, and examined its association to balance and prospective falls....

Immunotherapy with immune checkpoint inhibitors and immunotherapy combined with chemotherapy have represented promising treatments for NSCLC patients leading to prolonged survival. However, the majority of patients with advanced NSCLC have a poor prognosis. The identification and development of biomarkers for stratifying responders and non responders to immune checkpoint inhibitors contribute to unravel the mechanism of immune checkpoint pathway and the immune tumor interaction underlying the re...

BackgroundGlioblastoma (GBM), Isocitrate dehydrogenase-wildtype (IDH-wt) is characterised by diffuse infiltration, with progression often arising from perilesional tissue and occult white-matter damage. We investigated whether radiomics from the T2/FLAIR-defined oedema and the structural disconnectome improve prediction of progression-free survival (PFS). MethodsWe retrospectively analysed 387 adults with newly diagnosed GBM, IDH-wt treated at a single tertiary centre (2005-2020). A deep-learni...

Skeletal muscle metabolic and physical capacities are influenced by both genetics and load status and decline with age. Recent advances in sequencing have detailed cell types at unprecedented detail; yet these approaches do not scale to adequately model human muscle physiological heterogeneity. We produced a powerful resource for ageing studies, including consistent deep transcriptomic profiles of 1,675 human muscle biopsies ([~]28,000 genes per profile) and multiple single-cell spatial transcri...

Importance: Lung cancer mortality in the United States has fallen substantially in recent decades, yet the relative influence of behavioral, environmental, socioeconomic, and therapeutic factors and their sex specific contributions remains unclear. Understanding these drivers is essential to sustain progress and reduce persistent disparities. Objective: To quantify how behavioral, environmental, socioeconomic, and therapeutic determinants collectively shaped US lung cancer mortality from 1994 to...

Epigenetic clocks estimate biological age from DNA methylation patterns at CpG sites, providing robust predictions of mortality and morbidity risk. "Blue zones"--regions of exceptional longevity--offer a unique opportunity to investigate how biological aging diverges from chronological age. However, standard clocks are typically trained on large, heterogeneous datasets, reflecting average population trends rather than region-specific dynamics. Using data from the Costa Rican Longevity and Health...