Aging & Longevity

Natural killer (NK) cells exhibit remarkable adaptability within the tumour microenvironment (TME), where dynamic shifts in phenotype, function and metabolism govern their dual roles in antitumour immunity and tumour immune evasion. In the TME, NK cells undergo receptor remodelling, which is characterised by upregulated inhibitory signals and suppressed activating receptors, leading to the formation of dysfunctional subsets, such as exhausted TIM-3⁺ NK cells or tissue-resident CD49a⁺...

Triple-negative breast cancer (TNBC) is a highly aggressive subtype that currently lacks effective targeted therapies. Transcriptional co-regulator nuclear protein 1 (NUPR1) has been identified as a key stress-adaptive disordered protein that promotes tumor progression and therapy-induced resistance. In this study, we developed a robust high-throughput platform integrating in situ proximity ligation assay followed by DNA sequencing (isPLA-seq), NanoBiT assays, and C-degron degradation validation...

Neuronal hyperexcitability-defined as increased likelihood of action potential firing in response to stimuli-has emerged as a key pathophysiological feature in both normal aging and Alzheimer's disease (AD). This review synthesizes current evidence across species and models, evaluating the prevalence, mechanisms, and consequences of heightened excitability at the cellular and network levels. We examine electrophysiological and imaging-based indicators of hyperexcitability, including enhanced...

The primate brain possesses unique physiological and developmental features, yet its systematic investigation has been hampered by a paucity of transgenic germline models and tools. Here, we present a minimally invasive method to introduce transgenes widely across the primate cerebral cortex using ultrasound-guided fetal intracerebroventricular viral injections (FIVIs). FIVI enables efficient and long-lasting transgene expression following intrauterine delivery of recombinant adeno-associated...

Therapeutic biological scaffolds promote tissue repair primarily through the induction of type 2 immunity. However, systemic immunological factors, including aging, sex, and previous infections, can modulate this response. The gut microbiota is a well-established modulator of immune function across organ systems, yet its influence on type 2-mediated repair remains underexplored. Here, we establish a bidirectional relationship between the gut microbiota and biological scaffold-mediated tissue...

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CONCLUSION: We demonstrated the feasibility of OCSPlus administration by trained lay persons, its acceptability, and preliminary reliability and validity among low-literacy older adults on the Kenyan coast. Mean cognitive scores were mixed across the two groups. Cognitive performance was associated with several biopsychosocial factors spanning behavioural/lifestyle, sociodemographic, psychosocial, medical and treatment factors. Further validation studies and epidemiological research are needed...

CONCLUSION: TMAO-related metabolites consistently contributed positive SHAP effects, suggesting biologically relevant links between dietary metabolism and early cognitive decline. This interpretable ML framework offers a feasible, sensitive, and biologically informed approach for early MCI screening and supports the integration of nutritional biomarkers into cognitive health surveillance.

Transcranial alternating current stimulation (tACS) using a combined theta-gamma waveform can improve unilateral ballistic motor performance in the trained limb of older adults. The purpose of this study was to examine the effect of individual (theta) and combined (theta-gamma) tACS waveforms on ballistic motor performance in the trained and untrained contralateral limb (i.e. cross-limb transfer) of older adults. Sixty right-handed healthy older adults (68.9 ± 5.2 years) received either...

Aging is marked by progressive dysfunction in cellular maintenance pathways, including mitochondrial impairment, reduced autophagic capacity, and accumulation of senescent cells, which contribute to chronic low-grade inflammation. The transmembrane protein CD47 best known for delivering a "don't eat me" signal through SIRPα is increasingly recognized as an important modulator of several aging-related processes. Its upregulation in aged or inflamed tissues can inhibit the clearance of damaged or...

CONCLUSIONS: In the present study, TFE was shown to improve dexamethasone-induced muscle atrophy and degeneration in C2C12 myotubes, as evidenced by the restored expression of myogenic markers and the downregulation of atrophy-related genes and proteins. Additionally, TFE can attenuate sarcopenia progression in SAMP8 mice. Its effect was related to the regulation of the gut microbiota-bile acids-skeletal muscle axis.

CONCLUSIONS AND IMPLICATIONS: Lower predictive performance for rectal fever prediction in older adults supports using an oral threshold of 37.2 °C in high-risk hospitalized adults aged ≥75 years. Adjusting oral thresholds in older adults may improve infection detection and management.

Age-related hearing loss (ARHL) is a progressive, bilateral sensorineural impairment with significant socio-psychological consequences. Current ARHL models (natural aging or systemic D-galactose (D-gal) injection) face limitations: prolonged timelines, high variability, and inconsistent D-gal protocols. To concentrate aging pathology within the peripheral auditory system, we developed a novel accelerated cochlear aging model by targeted delivery of D-gal via the posterior semicircular canal....

CONCLUSIONS: Monitoring intrinsic capacity changes, especially locomotion decline, enables early identification of vulnerable older adults and supports timely, targeted interventions to reduce adverse outcomes.

The accelerating ageing of populations worldwide presents profound challenges for public health, particularly within long-term care facilities (LTCFs). Older adults, often burdened by multimorbidity, frailty, and immunosenescence, are highly vulnerable to vaccine-preventable diseases such as influenza, pneumococcal pneumonia, COVID-19, respiratory syncytial virus (RSV), pertussis, and herpes zoster (HZ). Despite the availability of effective vaccines, immunization coverage in LTCFs remains...

Iron homeostasis which is primarily regulated through intestinal iron absorption, is usually disrupted in the elderly. But changes of intestinal iron absorption with aging have not been elucidated. This study aims to investigate the role of intestinal iron absorption in driving age-related disruption of iron homeostasis. Male C57BL/6 J mice aged 2, 12, 18, and 24 months were utilized in this study to analyze age-related changes in systemic iron status, detect the alterations in intestinal iron...

Hydrogen sulfide is a gasotransmitter with biological functions, including roles in antioxidant defenses, mitochondrial bioenergetics, and cellular signaling via cysteine persulfidation. Several longevity-promoting interventions enhance endogenous hydrogen sulfide generation. However, whether enhanced hydrogen sulfide generation extends healthspan and lifespan in mammals remains unknown. Here, we investigated the in vivo effects of the non-enzymatic hydrogen sulfide generation promoted by...

Aging increases the risk of neurodegeneration, cognitive decline, and Alzheimer's disease (AD). We report that plasma concentrations of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and neurofilament light (NfL) become exponentially higher from ages 2 to 85 in cross-sectional samples, serving as neuronal death/damage biomarkers across the lifespan. UCH-L1 concentrations rise faster in females, who exhibit increased AD risk. Glial fibrillary acidic protein (GFAP) concentrations increase...

CONCLUSIONS AND IMPLICATIONS: A long sleep duration (≥9 hours) is a risk factor for a decline in walking speed among men aged 60 years and older. Routine assessment of sleep duration in primary care provides a low-cost, scalable strategy to identify older adults at risk and guide early interventions aimed at maintaining mobility and independence, especially among older men.

CONCLUSIONS: In later life, being frail does not necessarily imply low IC, and vice versa. Frailty and low IC identify different groups in early older age, but the overlap between them becomes more pronounced with increasing age. Comprehensive assessment of ageing therefore requires measures that capture both vulnerability to decline and capacity.