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CONCLUSIONS: Physical frailty was associated with lower IL-17 and higher TGF-β1 levels, suggesting that immune-related pathways beyond classical systemic inflammation may be associated with physical frailty. Rather than reflecting overt systemic inflammation, these findings suggest that biological pathways involved in immune regulation and tissue remodeling may be associated with physical frailty. IL-17 and TGF-β1 may therefore represent potentially informative biomarkers for future...

A new intranasal DNA vaccine may give the immune system an extra weapon against tuberculosis by targeting bacteria that can hide from antibiotics. In animal studies, it helped clear infections faster, reduced lung inflammation, and prevented relapse after treatment. The vaccine also enhanced the performance of drugs used against drug-resistant TB.

Using alcohol to cope with stress when young may permanently alter the brain, making it harder to adapt to challenges and increasing the risk of returning to drinking later in life. Researchers also found signs of brain damage associated with early dementia, suggesting the effects can linger long after alcohol use has stopped.

Some brains appear to fight back against Alzheimer's by helping immature brain cells survive damage instead of succumbing to it. Understanding this natural resilience could point researchers toward entirely new ways to protect memory and slow dementia.

Electroencephalography (EEG) slowing and reduced functional connectivity are markers of Alzheimer's disease (AD) and Lewy body dementia (DLB), but the significance of epileptiform discharges to these changes remains unknown. We investigated whether epileptiform discharges are associated with EEG slowing or decreased functional connectivity over time. In this longitudinal observational exploratory study, 15 healthy controls, 25 patients with AD, and 10 patients with DLB were included. Patients...

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss and behavioral changes. A pivotal influence on AD pathology is the dysregulation of microglia in the brain. Despite promising findings in mouse models, there are limitations to the translatable biological information across species due to differences in the physiology, timeline of disease, and human heterogeneity. To address these interspecies discrepancies, we developed a novel implementation of the...

Loneliness and social isolation increase the risk of physical and mental disorders in older adults, while resilience may mitigate this risk. The evidence that medial temporal lobe (MTL) structures are associated with loneliness, social isolation, and resilience is largely cross-sectional. This study examined whether baseline MTL structures were associated with loneliness, social isolation, or resilience during the COVID-19 pandemic. 114 older adults (59 females; mean age: 73.8 ± 5.6 years)...

Two principal strategies have gained prominence among currently recognised approaches to anti-ageing: systemic interventions that modulate the circulatory environment and cellular interventions that reset epigenetic information. Systemic approaches, beginning with experimental heterochronic parabiosis models that are not applicable to humans and extending to clinically applicable therapeutic plasma exchange, test the hypothesis that ageing is promoted by the accumulation of inhibitory...

Tumors reprogram lipid metabolism in distant tissues to support their growth. In adult Drosophila, gut tumors secrete the PDGF/VEGF-like factor Pvf1, which activates the TORC1-Hnf4 pathway in hepatocyte-like oenocytes. This drives production of very long-chain fatty acids and wax esters essential for tracheal growth around the tumor. Blocking Hnf4 or the elongase mElo in oenocytes strongly suppresses tracheogenesis, tumor progression, and cachexia-like organ wasting, while extending host...

Autosomal dominant mutations in TARDBP, encoding TAR DNA-binding protein 43 (TDP-43), cause amyotrophic lateral sclerosis (ALS), and TDP-43 pathology is a hallmark of multiple aging-associated neurodegenerative diseases. Despite its pathological role, effective therapies remain limited by the lack of safe, potent molecules targeting TDP-43 neurotoxicity. Here we show that the conserved α-helical region spanning residues 320-340 (conserved region or CR) is a therapeutically actionable target for...

Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address these questions, we performed transcriptomics, lipidomics and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of submaximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy...

The review summarizes the context-dependent role of enhancer of zeste homolog 2 (EZH2) in cellular senescence and aging-associated tissue dysfunction. It discusses a conceptual shift from strong pharmacological EZH2 inhibition toward a more nuanced, context-dependent epigenetic modulation by natural compounds. Aging is associated with tissue‑specific alterations in EZH2 expression-both its decline and overexpression have been linked to cellular senescence, impaired regeneration, and age‑related...

Idiopathic pulmonary fibrosis (IPF) is a paradigmatic aging-related lung disorder. In this retrospective cohort study, we evaluated 101 treatment-naïve patients at diagnosis (T0) and a subgroup (n = 31) after one year of antifibrotic therapy (T1). Analyses included leukocyte telomere length (LTL), DNA methylation age [DNAmAge assessed by Horvath, Levine (PhenoAge), Skin & Blood, Hannum, BLUP, Elastic Net (EN), and a 5-CpG panel], age acceleration (AgeAcc), and genetic susceptibility. At T1, LTL...

Aging profoundly remodels the immune system, impairing defense, repair and homeostatic function across tissues. Because the immune system operates in every organ, its deterioration has been proposed to drive or exacerbate systemic dysfunction and accelerate overall biological aging, making it an attractive biomarker and target for geroscience-guided trials. Despite this central role, there is no consensus on how to quantify immune aging, especially in clinical trials. Here, we establish a...

Liver aging is characterized by chronic inflammation and metabolic dysfunction that drive progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Necroptosis, a pro-inflammatory form of cell death via the Receptor-Interacting serine/threonine-Protein Kinase 1 (RIPK1)-RIPK3-Mixed Lineage kinase domain Like pseudokinase (MLKL) pathway, is activated in aging livers, and systemic inhibition of this pathway reduces hepatic inflammation and pathology. The cell type-specific...

CONCLUSIONS: This study revealed that nutritional status is independently associated with quality of life in older adults, independent of strong psychosocial determinants. Although depression, frailty, and loneliness were dominant predictors, the independent contribution of nutritional status suggests that nutritional assessment and interventions could be considered as an integral part of geriatric care. The findings highlight the potential role of comprehensive care models that combine...

CONCLUSIONS: Mutual aid among older residents was neither uniform across districts nor fixed over time. Rather, it was shaped by district-specific relational infrastructures and reconfigured through age-related changes in health, mobility, and everyday routines. Community interventions should therefore be tailored to the relational infrastructure already present in each district and should support modest, repeatable opportunities for reciprocal contact and gentle monitoring.

CONCLUSION: The present study highlights the substantial burden of malnutrition among older individuals. Two-thirds of the individuals were either at risk of developing malnutrition or had already developed malnutrition. As none of the sociodemographic factors were found to be associated, qualitative studies are needed to explore the various other reasons for developing malnutrition.

All animals age. However, aging is a heterogeneous process, and individual organisms age differently. Moreover, within the same organism, cells or organs do not age at the same speed. For instance, neurodegeneration, a hallmark of aging, generally manifests later than other peripheral aging signs. The genetic determinants of aging are not completely understood. Gain-of-function (GoF) mutations in leucine-rich repeat kinase 2 (LRRK2^(GoF)) are major genetic risk factors for Parkinson's disease...

The subthalamic nucleus (STN) is a prominent target for deep-brain stimulation (DBS) in the treatment of levodopa-induced dyskinesia (LID), a common motor complication of Parkinson's disease. However, the precise impact of STN-DBS on LID remains unclear. Here, we investigated the functional roles of two distinct neuronal populations within the STN in regulating LID. In a mouse model of LID, STN neurons projecting to the entopeduncular nucleus (EP) exhibited a U-shaped activation pattern, whereas...