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Spatial omics links molecular measurements to their positions in tissue, revealing cellular organization and interactions. Yet most computational tools highlight common cell types and overlook rare populations that can drive disease. Here we show GARDEN, a computational framework that identifies and characterizes these pathogenic cells or regions in spatial omics by embedding graph-based dynamic attention into a spatially-aware graph fusion contrastive model. GARDEN works consistently across...

CONCLUSIONS AND IMPLICATIONS: This review provides evidence of the relationship between housing and nursing home utilization; however, because of a weak quality of evidence and limited methodologic diversity, more research is needed to strengthen the evidence base. Clinicians, researchers, and policy makers should still recognize the significance of the role housing plays in nursing home utilization and target policies and interventions toward improving housing conditions for older adults and...

Epigenetic clocks are emerging as promising biomarkers of biological aging, yet their sensitivity to short-term interventions remains unclear. This pilot study investigates whether the GrimAge clock can capture the effects of a 6-month cycling-based endurance exercise training intervention, with cardiorespiratory fitness (VO(2) max) and body composition as primary outcomes. We enrolled 42 adults aged 35-65, of whom 38 completed the study and 33 adhered to the protocol (> 66% adherence)....

The interaction between nuclear (nDNA) and mitochondrial DNA (mtDNA) methylation is not well known in the healthy population. The D-loop methylation level of the Olympic champions (N = 58) was significantly lower than that of non-champions (N = 32) (~ 36% unadjusted mean difference p = 0.016, sex and age adjusted p = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, p = 0.033). On the other hand,...

Skin aging involves progressive structural and functional decline, yet the underlying molecular mechanisms remain unclear. Here, we report that the antimicrobial peptide S100A7 is markedly reduced in aged keratinocytes and that its depletion leads to transcriptional alterations in differentiation-, autophagy-, and senescence-associated pathways. S100A7 knockdown partially recapitulated senescence-associated signatures, whereas supplementation increased autophagy and attenuated senescence-like...

Within neurons, the misfolding and aggregation of certain proteins has been identified as a common feature of many late-onset neurodegenerative diseases (NDs). These aggregate-prone proteins include tau (in both primary tauopathies and in Alzheimer's disease) and alpha-synuclein in Parkinson's disease. There is strong experimental evidence that the upregulation of intracellular clearance pathways (autophagy and ubiquitin-proteasome pathways) can clear aggregate-prone proteins in experimental...

Parkinson's disease (PD) is a chronic neurological disorder characterized by loss of body movement control due to dopamine abnormalities. PD leads to various pathological symptoms, including muscle stiffness, bradykinesia, tremors, and postural disturbances. As a severe disease, PD caused approximately 329,000 deaths worldwide in 2019. However, PD treatment is very challenging; thus, alternative therapeutic strategies are in high demand. The primary therapeutic hurdle in PD therapy is the...

Parkinson's Disease (PD) is a neurodegenerative disorder primarily characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to classical motor symptoms such as tremors, rigidity, and bradykinesia. In later stages, patients frequently develop non-classical symptoms, including respiratory dysfunctions, which may result from neurodegeneration in brainstem regions involved in respiratory control, such as the pre-Bötzinger Complex (preBötC) and the retrotrapezoid...

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Frailty increasingly is recognized as a factor that modifies the relationship between disease biomarkers, including neuropathology, and dementia expression. The mechanisms underlying the relationship between frailty and dementia remain unclear, but blood biomarkers can offer insight into these mechanisms. We completed a scoping review of research examining the associations between blood biomarkers, frailty, and cognition. Three online databases were searched to identify original research...

Genome regulation is shaped not only by DNA sequence but also by epigenetic mechanisms that influence chromatin structure and gene expression. While epigenetics has classically focused on heritable DNA and histone modifications, growing evidence indicates that certain forms of DNA damage can also generate persistent changes in transcriptional states that are heritable in some scenarios. This review examines how diverse DNA damage-associated processes-including oxidative lesions, R-loops,...

CONCLUSIONS AND IMPLICATIONS: Higher total sugar intake and moderate added sugar intake were associated with lower frailty risk in older Korean adults. These findings highlight the importance of considering both the amount and source of dietary sugars when developing nutritional guidelines for healthy aging. Future policies should focus on nuanced dietary recommendations rather than universal restriction for the elderly population.

Protein misfolding and aggregation are cardinal features of neurodegenerative disease (NDD) and they contribute to pathophysiology by both loss-of-function (LOF) and gain-of-function (GOF) mechanisms. This is well exemplified by TDP-43 which aggregates and mislocalizes in several NDDs. The depletion of nuclear TDP-43 leads to reduction in its normal function in RNA metabolism and the cytoplasmic accumulation of TDP-43 leads to aberrant protein homeostasis. A modifier screen found that loss of...

Evidence suggests that cancer-related accelerated aging contributes to an earlier onset of chronic diseases; persistent symptoms; and decrements in patients' quality of life. This review presents the Multifactorial Model of Cancer-related Accelerated Aging (MMCRAA), a conceptual framework that is grounded in Life Course Theory and supported by empiric evidence. The model includes six inter-related concepts: person, behavioral, biological, treatment, symptom, and life course factors. The MMCRAA...

Chronic inflammation promotes aging and age-associated diseases. While metabolic interventions can modulate inflammation, how metabolism and inflammation are connected remains unclear. Cytoplasmic chromatin fragments (CCFs) drive chronic inflammation through the cGAS-STING pathway in senescence and aging. However, CCFs are larger than nuclear pores, and how they translocate from the nucleus to the cytoplasm remains uncharacterized. Here we report that chromatin fragments exit the nucleus via...

CONCLUSIONS: A sense of physical and mental health has a key impact on SA. Important moderators of SA include individual agency, sociodemographic factors, and, in particular, education level and household type. Due to the difficulties in defining unambiguous quality criteria, SA should be treated as a linear variable.

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Aging of the blood system impacts systemic health and can be traced to hematopoietic stem cells (HSCs). Despite multiple reports on human HSC aging, a unified map detailing their molecular age-related changes is lacking. We developed a consensus map of gene expression in HSCs by integrating seven single-cell datasets. This map reveals previously unappreciated heterogeneity within the HSC population. It also links inflammatory pathway activation (TNF/NFκB, AP-1) and quiescence within a single...

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...

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