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Cellular senescence contributes to inflammaging in part through the senescence-associated secretory phenotype (SASP). R-loops, three-stranded nucleic acid structures, contribute to innate immune response in cancers; however, the role of R-loops in senescence and inflammaging remains largely unknown. Here we show that nuclear-derived cytoplasmic R-loops promote the SASP and inflammaging. We detect an accumulation of nuclear-derived R-loops in the cytoplasm of senescent cells with an enrichment in...

Intrinsic capacity (IC) is a key construct within the healthy ageing framework. However, the correlations among IC domains and their association with health outcomes in very old adults remain unclear. This study aimed to characterise the relationships among IC domains using network analysis and to examine their association with mortality in community-dwelling octogenarians from the Invecchiamento e Longevità nel Sirente (ilSIRENTE) cohort. IC was calculated as a summary score rescaled to a 0-100...

Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia, yet sensitive behavioral and neural markers of early cognitive decline remain to be fully characterized. Increasing evidence suggests that instability of proactive control mechanisms, rather than generalized slowing, may play a critical role in early cognitive impairment. The present study investigated whether behavioral variability and preparatory neural activity constitute neurobehavioral markers...

Cardiovascular-Kidney-Metabolic (CKM) syndrome is uncharacterized in Chinese adults across ages, including centenarians. From three cohorts, age- and sex-standardized CKM prevalence showed nearly 90% stage≥1 and >18% advanced. Prevalence rose with age; advanced CKM reached 100% in male centenarians. Age, sex, smoking, and BMI were risk factors for advanced CKM, with faster male progression. These findings highlight growing disease burden in China's aging population and inform future CKM...

Aging clocks are tools that quantify biological aging through the integration of multi-omics data, encompassing epigenetic, transcriptomic, proteomic, metabolic, and microbial information, together with functional biomarkers. These tools show significant potential for use in preventive medicine, early detection of chronic conditions, and monitoring the effectiveness of interventions designed to enhance population health. The advancement of artificial intelligence has facilitated the widespread...

Microtubules are dynamic cytoskeletal polymers whose lattice architecture regulates force generation, nucleotide hydrolysis, and recognition by motor proteins and microtubule-associated proteins (MAPs). Microtubule-stabilizing agents (MSAs), including taxanes and laulimalide/peloruside-site ligands, suppress depolymerization by binding to defined lattice sites, yet stabilization is not structurally neutral. How ligand chemistry reshapes lattice organization and function remains unresolved. Here,...

Despite the effectiveness of combined antiretroviral therapy (ART), HIV infection remains a chronic condition characterised by persistent inflammation and immune activation, likely associated with viral persistence and other factors such as cytomegalovirus (CMV) co-infection. Long-acting (LA) injectable formulations, a newer class of ART with improved and sustained bioavailability, may help modulate the HIV-associated immunoinflammatory state. Therefore, we analysed dynamic changes in lymphoid...

The growing burden of aging-related disease and functional decline across Europe underscores the urgent need to optimize aging trajectories rather than simply extend lifespan. Achieving this goal requires identifying modifiable determinants that shape biological, psychological, and functional aging across the life course. Satisfaction with life (SWL) is emerging as one such integrative factor, linking adaptive capacity, resilience, and long-term healthspan outcomes. In this conceptual and...

Transcription by RNA polymerase II (RNAPII), which is essential for protein-coding gene expression and cellular function, is increasingly understood to become dysregulated with aging. Here, we use a multimodal approach to comprehensively characterize age-dependent changes in RNAPII-mediated transcription in both mouse and human tissues. Short-read total RNA sequencing (RNA-seq) to profile nascent transcription reveals a global reduction in overall transcriptional activity/frequency in aged...

Microbiota-derived metabolites are central mediators between commensal microbes and host immune system at mucosal barrier surfaces. Insights from mouse models have revealed precise molecular mechanisms by which numerous metabolites, including short-chain fatty acids, tryptophan catabolites and bile acid derivatives, regulate epithelial integrity, innate immune tone, and adaptive immunity and tolerance. Parallel studies in humans increasingly confirm these pathways and link metabolite...

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Alzheimer's disease (AD) progresses along a continuum for years to possibly decades prior to cognitive decline. Although AD is primarily an age-related brain pathology, increasing evidence indicates dysfunction in peripheral nerves and skeletal muscle may manifest early in the disease progression. However, the underlying cause(s) for peripheral nerve dysfunction leading to impaired skeletal muscle torque production are not understood. Sciatic nerves from 5xFAD and wild-type (WT) mice were...

CONCLUSIONS: In the multimorbidity management model for older adults, interventions such as patient peer support groups and case manager-led health education are proposed as theoretical strategies. These potential measures aim to support patient self-efficacy and facilitate health literacy, thereby potentially contributing to better overall health of patients.

CONCLUSIONS: There are distinct joint trajectories of physical frailty and social relationships among Japanese community-dwelling older adults. These trajectories are associated with different risks of long-term care needs, with the progressive frailty and rapid social relationships decline subgroup facing the greatest burden.

Macrophages are pivotal immune cells due to their phagocytic capabilities, yet the impact of aging on macrophage phagocytosis remains poorly understood. Using comprehensive in vitro and in vivo phagocytic assays, we demonstrate significantly reduced phagocytic activity in monocyte-derived macrophages from aged humans and mice compared to young counterparts. RNA-seq analysis revealed upregulated expression of extracellular matrix protein genes, particularly collagens, in aged macrophages;...

Myofibroblasts are morphologically similar cells with diverse origins that exhibit characteristics of both fibroblasts and smooth muscle cells. Following insults, myofibroblasts play critical roles in tissue reintegration and restitution. However, their prolonged presence and activity impede physiological recovery, leading to persistent or progressive tissue complications, as evidenced in corneal fibrosis and opacification. Reactive oxygen species (ROS) are key signaling intermediates in various...

Humans evolved to pay close attention to danger, but today that instinct is being overwhelmed by an endless supply of bad news from around the world. Researchers say the answer isn’t to stop following current events—it’s to build healthier habits around how, when, and where we get our news.