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RNA-binding proteins and ribonucleoproteins as determinants of immunity
Infection triggers one of the most dramatic systemic responses in the body, and the coordinated activation and function of immune cells requires a dynamic regulation of transcriptomes and proteomes. This is achieved by RNA-binding proteins, which, together with RNA, form ribonucleoproteins. These proteins expand the information content of the genome and determine the lifespan, localization and function of RNA. Moreover, they control when, where and how much protein is produced. They can also...
GLP-1 receptor agonism counteracts omics aging in mice
No abstract
DNA damage in macrophages drives immune autoreactivity via nuclear antigen presentation
Aging and DNA damage increase the risk of chronic inflammation and autoimmunity, yet the molecular underpinnings remain unclear. In this study, we uncover a DNA damage-driven mechanism in macrophages that triggers immune autoreactivity. Here, using Er1^(Lyz2/)^(-) mice with a macrophage-specific DNA repair defect in ERCC1-XPF, we demonstrate that monocyte-derived macrophages accumulate DNA damage, activate the immune system, drive polyclonal T cell responses and generate antinuclear...
The development of a method to activate vital communities, facilitation of older people ageing in place: a community-based participatory research
CONCLUSION: Community activation is a complex, multidisciplinary process that requires inclusive collaboration and local ownership. The Community Activation Compass offers a promising framework to guide such efforts, but further implementation and evaluation are needed to assess its impact on ageing in place.
Aging of the Hematopoietic System: Mechanisms, Consequences, and Systemic Interactions
The aging of the hematopoietic system is central to physiological aging, with profound consequences for immune competence, tissue regeneration, and systemic health. Age-related changes manifest as altered blood cell composition, functional decline in hematopoietic stem cells (HSCs), and deterioration of the bone marrow niche. Beyond hematologic dysfunction, hematopoietic aging acts as a systemic amplifier of age-related diseases through clonal hematopoiesis and inflammatory remodeling. This...
From breath to brain: influenza vaccination as a pragmatic strategy for dementia prevention
Aging populations require scalable strategies to delay or prevent dementia. Beyond the prevention of neurological injury associated with seasonal influenza, vaccination may help mitigate vascular and neuroinflammatory injury underlying cognitive impairment. Influenza infection can cause a marked short‑term increase in myocardial infarction risk, and acute infections have also been associated with transient increases in stroke risk. Experimental models show prolonged microglial activation and...
G1/S arrest: a key mechanism of cellular aging and replicative senescence
Replicative senescence frequently occurs in in vitro cell cultures and certain in vivo pathological conditions, characterized by multiple phenotypes, including cell cycle arrest. Previous studies suggested that the main mechanism underlying replicative senescence is that under continuous subculture, cells sense DNA damage during G1, which triggers G1/S arrest and the subsequent geroconversion. However, this explanation does not account for phenomena such as how DNA damage caused by replication...
External validation of geriatric influenza death score: a prospective validation study
CONCLUSION: In summary, the GID score offers a practical and efficient method for predicting 30-day mortality and informing disposition decisions for older ED patients with influenza.
Lipid-laden endothelial cells exhibit a transcriptomic signature linked to blood-brain barrier dysfunction, metabolic reprogramming, and increased inflammation in the aging brain
Dysregulation in lipid metabolism is increasingly recognized as a key contributor to age-related diseases, including neurodegeneration and cerebrovascular dysfunction. While prior studies have largely focused on glial cells, the impact of lipid dysregulation on brain endothelial aging remains poorly understood. In this study, we conducted a secondary analysis of single-cell transcriptomic data from young and aged mouse brains, with a specific focus on endothelial cells (ECs). Our analyses...
Metacontrol-related aperiodic and periodic neural activity in cognitive aging: enhancing the neural signal-to-noise ratio through anodal transcranial direct current stimulation
Metacontrol, the ability to adapt cognitive control to task demands, declines with age and is thought to be reflected in aperiodic and periodic neural dynamics. Given that anodal transcranial direct current stimulation (atDCS) can modulate cortical excitability via membrane potential shifts, we tested whether atDCS alters the neurophysiological signatures of metacontrol in younger and older adults. In a mixed design, younger and older participants performed a Go/Nogo task under both atDCS and...
Molecular underpinnings of induced degenerative heterogeneity in the retinal pigment epithelium
Cigarette smoking induces epigenetic changes that can cause degenerative heterogeneity with aging and disease. In disease such as age-related macular degeneration (AMD), the leading worldwide cause of blindness among the elderly, retinal pigment epithelial (RPE) cell heterogeneity is a key change. Since smoking is a powerful risk factor for AMD, we hypothesized that smoke induces epigenetic-mediated degenerative RPE heterogeneity. We administered cigarette smoke condensate (CSC) to young and...
Proteasomal proteolysis in p62 condensates directs tumor suppression or growth depending on their subcellular localization
p62/SQSTM1 generates liquid-liquid phase-separated condensates that participate in diverse processes, including protein quality control (PQC) and autophagy. Nuclear p62 condensates were shown to act as ubiquitin- and proteasome-mediated degradation hubs, whereas the involvement of cytoplasmic condensates in this pathway has remained unclear. Here, we show that cytoplasmic p62 condensates serve as a hub for proteasomal degradation that displays distinct substrate preferences compared with nuclear...
NNMT inhibition counteracts tubular senescence and fibrosis in early stages of chronic kidney disease
Chronic kidney disease (CKD) is projected to become the fifth leading cause of mortality by 2040. Tubular senescence drives kidney fibrosis, but current treatments do not target senescent cells. Here, we identify nicotinamide-N-methyltransferase (NNMT) as a critical mediator of tubular senescence and kidney fibrosis. Human CKD microarrays link NNMT to senescence and fibrosis transcriptomic signatures, and diabetic kidney disease (DKD) biopsies show NNMT protein associating with p21, fibrosis,...
Using monitoring technologies to care for older persons: Findings from a cross-sectional survey in Switzerland
CONCLUSIONS: Higher acceptance was found for smart wearable devices for elder care purposes compared to the sensors and cameras at home. Presence of actual need such as risk of falling, practical care situations, as well as an overall emphasis on ensuring the safety of older persons, were observed to positively impact the acceptance of technologies. Our findings also impart significance of the role of caregiving stress as a driver to incorporating technical tools in elder care. Further research...
Microbiota-derived indole-3-propionic acid extends lifespan in Drosophila and improves muscle and bone health in mice
Aging is associated with alterations in endogenous tryptophan (TRP) metabolism that contributes to musculoskeletal decline. In this study, we investigated the effects of the microbiota-derived TRP metabolite, indole-3-propionic acid (IPA), on musculoskeletal health in aged mice and lifespan in Drosophila melanogaster. Aged C57BL/6 mice received IPA (20 mg/kg, subcutaneous, three times per week for 12 weeks), while Drosophila were maintained on food supplemented with IPA (100 µM) throughout their...