Aging & Longevity

Despite systemic viral suppression, people living with HIV (PLHIV) on antiretroviral therapy (ART) remain highly susceptible to pneumococcal colonisation and disease. Here, we show that long-term ART does not restore nasal mucosal immunity. Using flow cytometry, single-cell transcriptomics, and neutrophil functional assays, we identify a persistent mucosal immune signature in PLHIV-ART > 1 yr marked by epithelial-driven neutrophilic inflammation, T cell exhaustion, and cellular senescence....

CONCLUSIONS: Older adult's functional limitations and negative generalization of ageing may have prevented them from actively seeking health information and health-promoting behaviors. To enhance the intervention's effectiveness, the health education contents should be customized based on their health needs, functional capabilities, and readiness to change health behaviors.

We aimed to develop and validate a urinary miRNA aging clock, positioning urine as a scalable, non-invasive aging-biomarker source. Using machine learning on 6331 adults, our clock achieved MAE ≈ 4.4 years (R² ≈ 0.79) in independent validation. The clock's key biomarkers included well-established geromiRs miR-34a-5p, miR-31-5p, miR-146a-5p, and miR-155-5p. While slightly less accurate than DNA-methylation clocks, our model outperformed blood-based miRNA and mRNA clocks, underscoring urinary...

Aging is characterized by amplified inflammation, including proinflammatory macrophages and increased susceptibility to endotoxemia. Here we uncover a mechanism by which macrophages maintain their inflammatory phenotype through autocrine GDF3-SMAD2/3 signaling, which ultimately exacerbates endotoxemia. We show that inflammatory adipose tissue macrophages display an age-dependent increase in GDF3, a TGFβ-family cytokine. Lifelong systemic or myeloid-specific Gdf3 deletion leads to reduced...

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CONCLUSION: There was an association between depressive moods and oral frailty. In addition, a relationship between depressive moods and subjective oral dysfunction, such as chewing ability and dryness, was observed.

Oxytocin, a hormone linked to reproduction and health, may mediate life-history trade-offs across the human life course. Yet, how oxytocin naturally varies with age remains poorly understood. Here, working with the Tsimane, forager-horticulturalists of lowland Bolivia, we collected the largest sample of oxytocin measurements to date (n = 1,242 samples, n = 405 individuals, age = 2 to 84 y, 51% female), and i) examined how oxytocin varies throughout the life course in females and males, and ii)...

CONCLUSION: In this preliminary study, we observed a strong association between CSF Klotho levels and CP enlargement. Reduced CSF Klotho levels, due to CP dysfunction, may contribute to neurodegeneration. If confirmed in larger cohorts, this association suggests that CSF Klotho may serve as a biomarker for CP enlargement, possibly reflecting its underlying dysfunction.

Tests that can predict whether a drug is likely to extend mouse lifespan could speed up the search for anti-aging drugs. We have applied a machine learning algorithm, XGBoost regression, to seek sets of plasma metabolites (n = 12,000) and peptides (n = 17,000) that can discriminate control mice from mice treated with one of five anti-aging interventions (n = 278 mice). When the model is trained on any four of these five interventions, it predicts significantly higher lifespan extension in mice...

As a target organ in direct contact with external air, lung tissue is more susceptible to aging, and lung aging is closely related to the development of chronic lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis. Evolutionarily speaking, the Wnt signaling pathway is highly conserved and plays an important role in embryonic development, tissue homeostasis, as well as cell proliferation, differentiation, apoptosis, and migration of a variety of cells. Alterations in...

Human brain aging involves a variety of cellular and synaptic changes, but how these changes affect brain function and signals remains poorly understood due to experimental limitations in humans, meriting the use of detailed computational models. We identified key human cellular and synaptic changes occurring with age from previous studies, including a loss of inhibitory cells, NMDA receptors, and spines. We integrated these changes into our detailed human cortical microcircuit models and...

The accumulation of α-synuclein (α-syn) is a key pathophysiological feature of Parkinson's disease (PD), and one contributing factor to this aggregation is impaired clearance mechanisms. Recent research has identified the glymphatic system as the brain's intrinsic waste clearance pathway. This review examines glymphatic dysfunction in PD, with a focus on its impact on α-syn clearance and neurodegeneration. We summarize current evidence showing that disrupted aquaporin-4 (AQP4) polarization,...

Mitochondria play a central role in metabolism and biosynthesis, but function also as platforms that perceive and communicate environmental and physiological stressors to the nucleus and distal tissues. Systemic mitochondrial signaling is thought to synchronize and amplify stress responses throughout the whole body, but during severe or chronic damage, overactivation of mitochondrial stress pathways may be maladaptive and exacerbate aging and metabolic disorders. Here we uncover a protective...

Cochlear nerve demyelination is a significant pathogenic factor of age-related hearing loss (ARHL), and Schwann cell (SC) migration function plays a key role in the maintenance and regeneration of myelin sheaths. Here, we found that bone marrow stromal antigen 2 (BST2) is significantly upregulated in cochlear SCs during aging following demyelination and hearing loss. However, specific knockdown of BST2 in SCs could obviously improve the SCs migration and the myelin sheath structure manifested in...

Targeting senescent pancreatic β-cells represents a promising therapeutic avenue for age-related diabetes; however, current anti-senescence strategies often compromise β-cell mass. In this study, human amniotic mesenchymal stem cell-derived small extracellular vesicles (hAMSC-sEVs) were identified as a novel intervention that can be used to effectively counteract cellular senescence and preserve β-cell integrity. We aimed to systemically delineate the molecular mechanisms underlying...

This paper focuses specifically on the education and upskilling of medical doctors, proposing how longevity-related competencies can be incorporated first through continuing medical education (CME) pathways and, eventually, into formal medical curricula. As longevity medicine evolves from research into clinical practice, education has emerged as its defining challenge. While the science of ageing advances rapidly, most physicians remain unprepared to translate biological, technological, and...

This study aims to analyze the global research landscape and identify emerging trends in research hotspots, key technologies, and clinical applications in proteomics research in aging from 1998 to June 20, 2025. Publications related to aging and proteomics from 1998 to June 20, 2025 were retrieved from the Web of Science Core Collection. A bibliometric analysis was conducted using VOSviewer, CiteSpace, and R 4.3.3 to evaluate publication trends, research collaborations, and emerging topics. A...

Central to the legume-rhizobium symbiosis is the formation of organelle-like symbiosomes where nitrogen-fixing bacteroids are enclosed by a host-derived symbiosome membrane. This creates the symbiosome space, which topologically resembles an apoplastic compartment within the cell. While the apoplast of plant cells is largely occupied by the cell wall, symbiosomes are devoid of cell wall polymers. Here, we describe a mechanism that functions to protect and maintain effective nitrogen fixation...

Aging is associated with declines in physical, cognitive, and physical and mental well-being. This randomized trial aimed to assess the effects of a supervised, home-based multicomponent physical training program delivered via videoconferencing on physical fitness, cognitive performance, and mental well-being in healthy older adults. Thirty participants aged 60-70 years completed either a physical training intervention (PT), a health education intervention (active control, AC), or no...

Cognitive decline is one of the key challenges with aging, with significant implications for independence, quality of life, and healthcare burden. As pharmacological treatments remain limited in efficacy and often carry adverse effects, there is growing interest in safe, accessible, non-pharmacological strategies to preserve cognitive function. This Short Review explores the potential of combining two approaches that, individually, have shown beneficial effects on cognitive function:...