In-vivo Transcriptomic Profiling of Systemic Aging using Stem Cell Encapsulation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA436920 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Sustained exposure to a young systemic environment rejuvenates aged tissues and promotes stem cell function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint direct effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human stem cells in highly diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging independent of physical cellular interactions in-vivo.
2022-03-05 | GSE111401 | GEO
Project description:Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.
2022-03-05 | GSE193665 | GEO
Project description:In Vivo Transcriptomic Profiling using Cell Encapsulation Identifies Effector Pathways of Systemic Aging
| PRJNA797090 | ENA
Project description: Not available
| S-EPMC8926399 | biostudies-literature
Project description:Age-related microvascular dysfunction disrupts nutrient homeostasis and waste clearance, leading to organ failure. However, a critical gap remains in our understanding of the specific molecular drivers of vascular deterioration and how they orchestrate organism-wide aging. Here, we identify progressive activation of the CCAAT/enhancer-binding protein β (C/EBPβ)/asparagine endopeptidase (AEP) pathway in aging vascular endothelial cells contributes to vascular degeneration and lifespan reduction. Endothelial-specific C/EBPβ or AEP overexpression accelerated vascular aging and shortened lifespan in mice. Mechanistically, AEP mediates proteolytic cleavage of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (oxidised form, NAD+) biosynthesis, resulting in systemic NAD⁺ depletion and senescence that elicits both central and peripheral vascular dysfunction and ultimately systemic aging. Genetic ablation of AEP or expression of AEP-resistant NAMPT N136A mutant significantly ameliorated vascular aging and extended lifespan in endothelial-specific Tie 2-C/EBPβ transgenic mice. Pharmacologically, AEP inhibitor CP#11A or nicotinamide mononucleotide (NMN) supplementation alleviated age-related vascular decline, with CP#11A showing superior efficacy. These findings support a model in which endothelial senescence contributes to vascular dysfunction and systemic aging mediated by C/EBPβ/AEP signaling, and establish C/EBPβ/AEP as a therapeutic target to preserve vascular integrity and mitigate systemic frailty in aging populations.
2026-05-30 | E-MTAB-17006 | biostudies-arrayexpress
Project description:HuR coordinates systemic aging through platelet infiltration
| PRJNA1184739 | ENA
Project description:Aging is characterized by degeneration of unique tissues. However, dissecting the interconnectedness of tissue aging remains a challenge. Here, we employ a muscle-specific DNA damage model in Drosophila to reveal secreted factors that influence systemic aging in distal tissues. Utilizing this model, we uncovered a cytokine, Diedel, that when secreted from muscle or adipose can attenuate age-related intestinal tissue degeneration by promoting proliferative homeostasis of stem cells. Diedel is both necessary and sufficient to limit tissue degeneration and extend lifespan. Secreted homologs of Diedel are also found in viruses, having been acquired from host genomes. Focusing on potential mechanistic overlap between cellular aging and viral-host cell interactions and, we found that Diedel is a functionally conserved inhibitor of apoptosis and can act as a systemic rheostat to modulate cell death during aging. These results highlight a key role for secreted antagonists of apoptosis in the systemic coordination of tissue aging.
2018-07-02 | GSE111248 | GEO
Project description:Aging involves morphological and functional changes across different organs, but how these changes are linked among the different organs remains to be elucidated. Here, we uncover a central role of platelets in sys temic aging. In aged mice, the levels of platelet secreted pro inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in brain, liver, lung, kidney, and aortic root. The RNA binding protein HuR/ELAVL1, a major regulator of R NA metabolism, promoted the production of PSPF in platelets. Platelet specific deletion of HuR reduced the expression of PSPF in platelets, alleviated platelet infiltration in brain, liver, lung, kidney, and aortic root, and delayed systemic aging. Our findings highlight a role of platelets in coordinating aging traits across organs.
2024-11-16 | GSE281572 | GEO
Project description:Red blood cells (RBC) can act as carriers for therapeutic agents and given their biocompatibility and long lifespan in the circulation, they can substantially improve the safety, pharmacokinetics, and pharmacodynamics of many drugs. Maintaining RBC integrity and lifespan is important for the efficacy of RBC as drug carrier and can be a complex challenge of drug encapsulation. We investigated the impact of drug encapsulation by hypotonic dialysis on RBC physiology and integrity. Several parameters were compared between processed RBC loaded with L-asparaginase (“eryaspase�), processed RBC without drug and non-processed RBC. Processed RBC were less hydrated and displayed a reduction of intracellular content, relative to non-processed RBC. This reduction of intracellular content changed the RBC metabolomic profile, as indicated by the activation of the pentose phosphate pathway, but no impact on the global RBC proteomic profile was observed. We found that the encapsulation process caused moderate morphological changes and was accompanied by an increase of microparticles. Despite a decrease in their deformability, processed RBC were not mechanically retained in a spleen-mimicking device. Moreover, processed RBC had increased surface-to-volume ratio and osmotic resistance. Finally, the half-life of processed RBC was not significantly affected in a mouse model and our previous phase 1 clinical study showed that encapsulation of asparaginase in RBC prolonged its in vivo half-life compared to free form. Overall, our study demonstrated that encapsulation by hypotonic dialysis may affect certain several characteristics of RBC, but does not significantly impact on the in vivo longevity of RBC or their drug carrier function.
2021-11-29 | PXD022549 | Pride
Project description:In the general human population, aging is associated with a rise in systemic inflammation, primarily involving innate immune pathways related to interferon (IFN), toll-like receptor, and cytokine signaling. In systemic lupus erythematosus (SLE), a prototypical systemic autoimmune disease, aging is distinctly associated with improvements in disease activity, suggesting a unique relationship between aging and inflammation in this disease. Using a multi-omic approach incorporating transcriptional profiling, single cell RNA sequencing and methylation analysis, we studied age-related changes in the immune profiles of 287 SLE patients between 20 and 83 years old, and compared the results against 928 healthy controls aged between 21 and 89 years old. In contrast to the increase in inflammatory gene expression that occurs with aging in most healthy adults, SLE patients exhibited the opposite. Most notable was a decrease in type I and II IFN signaling that was evident across multiple cell types, with natural killer (NK), CD4+ effector memory T cells, and naïve B cells exhibiting the most significant differences. We found that aging in SLE patients was also associated with differential methylation of the genome. Notably, of the genes both downregulated and hypermethylated with older age, IFN-related genes were disproportionately represented, suggesting that age-related decreases in IFN signaling were driven in part by epigenetic silencing. Both SLE patients and healthy controls demonstrated age-related declines in naïve T cells and lymphoid progenitor cells, but only SLE patients demonstrated age-related increases in CD56-dim NK cells. Taken together, our work provides new insight into the phenomenon of inflammaging and the unique clinical improvement in disease activity that occurs in SLE patients as they age.
2025-06-26 | GSE277909 | GEO