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Continuous map of early hematopoietic stem cell differentiation across human lifetime

3 weeks 6 days ago
Uncovering early gene network changes of human hematopoietic stem cells (HSCs) leading to differentiation induction is of utmost importance for therapeutic manipulation. We employed single cell proteo-transcriptomic sequencing to FACS-enriched bone marrow hematopoietic stem and progenitor cells (HSPCs) from 15 healthy donors. Pseudotime analysis reveals four major differentiation trajectories, which remain consistent upon aging, with an early branching point into megakaryocyte-erythroid...
Hana Komic

An obesogenic FTO allele causes accelerated development, growth and insulin resistance in human skeletal muscle cells

3 weeks 6 days ago
Human GWAS have shown that obesogenic FTO polymorphisms correlate with lean mass, but the mechanisms have remained unclear. It is counterintuitive because lean mass is inversely correlated with obesity and metabolic diseases. Here, we use CRISPR to knock-in FTO^(rs9939609-A) into hESC-derived tissue models, to elucidate potentially hidden roles of FTO during development. We find that among human tissues, FTO^(rs9939609-A) most robustly affect human muscle progenitors' proliferation,...
Lu Guang

Senescent-like microglia limit remyelination through the senescence associated secretory phenotype

3 weeks 6 days ago
The capacity to regenerate myelin in the central nervous system diminishes with age. This decline is particularly evident in multiple sclerosis (MS), a chronic demyelinating disease. Whether cellular senescence, a hallmark of aging, contributes to remyelination impairment remains unknown. Here, we show that senescent cells accumulate within demyelinated lesions after injury, and treatments with senolytics enhances remyelination in young and middle-aged mice but not aged mice. In young mice, we...
Phillip S Gross

A torpor-like state in mice slows blood epigenetic aging and prolongs healthspan

3 weeks 6 days ago
Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase healthspan, remain unknown. Here we demonstrate that the activity of a spatially defined neuronal population in the preoptic area, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a...
Lorna Jayne

An analysis of curative care expenditure for Parkinson's disease under different comorbidity conditions: an empirical study based on China

3 weeks 6 days ago
CONCLUSIONS: The CCE for PD is high, and individuals and families are the main bearers of health expenditures. It is recommended to optimize medical insurance policies, increase outpatient insurance coverage, and gradually increase the level of insurance benefits. Furthermore, it is necessary to explore multi-party collaboration to establish a diversified and multi-level medical security system for PD.
Yuelin Zhou

Citrulline regulates macrophage metabolism and inflammation to counter aging in mice

3 weeks 6 days ago
Metabolic dysregulation and altered metabolite concentrations are widely recognized as key characteristics of aging. Comprehensive exploration of endogenous metabolites that drive aging remains insufficient. Here, we conducted an untargeted metabolomics analysis of aging mice, revealing citrulline as a consistently down-regulated metabolite associated with aging. Systematic investigations demonstrated that citrulline exhibited antiaging effects by reducing cellular senescence, protecting against...
Zhangdan Xie

Lifestyles and their relative contribution to biological aging across multiple-organ systems: Change analysis from the China Multi-Ethnic Cohort study

3 weeks 6 days ago
CONCLUSIONS: Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.
Yuan Zhang

An explainable machine learning-based prediction model for sarcopenia in elderly Chinese people with knee osteoarthritis

3 weeks 6 days ago
CONCLUSION: From the perspective of public health and aging, this study constructed an interpretable sarcopenia risk prediction model on the basis of routine clinical data. This model can be used for early screening and risk assessment of symptomatic KOA patients, assisting health departments and clinicians in the early detection and follow-up of relevant populations, thereby improving the quality of life and health outcomes of elderly individuals.
Ziyan Wang

Aged regulatory T cells fail to control autoimmune lacrimal gland pathogenic CD4<sup>+</sup> T cells

3 weeks 6 days ago
CD25KO mice are a model of Sjögren disease. CD25KO mice have severe inflammation and infiltrating lymphocytes to the lacrimal glands (LG). Whether the pathogenicity of CD25KO CD4^(+) T cells can be controlled in vivo by Tregs is unknown. Eight-week-old B6 and CD25KO mice LGs were submitted for RNA bulk sequencing. A total of 3481 genes were differentially expressed in CD25KO LG compared to B6. Tear washing analysis identified CD25KO mice had elevated protein levels of TNF, IFN-γ, and CCL5 and...
Kaitlin K Scholand

A Single-Cell Transcriptome Atlas Characterizes the Immune Landscape of Human Testes During Aging

3 weeks 6 days ago
Aging disrupts immune regulation, affecting tissue function and increasing vulnerability to various diseases. However, the effects of aging on immune cells within human testes are not well understood. In this study, we utilized single-cell RNA sequencing to profile immune cells from 33 human testis samples from individuals aged 21 to 69. Our analysis revealed key immune cell types, including CD8^(+) T cells, monocytes, cDC2 cells, and various macrophage subtypes within the testes. We observed an...
Qiaoling Jiang

Prediction of hearing aid cognitive outcomes in age-related hearing loss

3 weeks 6 days ago
Although the phenomena underlying cognitive decline and dementia are complex, there is growing evidence suggesting that degraded sensory inputs caused by age-related hearing loss may play a central role in accelerating cognitive decline in older individuals. Further supporting this notion is evidence that hearing augmentation with hearing aids can mitigate hearing loss-related cognitive impairments. Despite this evidence, few studies have attempted to investigate hearing aid efficacy with a...
Patrice Voss