Browse
Submit Data
Databases
API
Help

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An aged immune system drives senescence and ageing of solid organs.

ABSTRACT: Ageing of the immune system, or immunosenescence, contributes to the morbidity and mortality of the elderly^1,2. To define the contribution of immune system ageing to organism ageing, here we selectively deleted Ercc1, which encodes a crucial DNA repair protein^3,4, in mouse haematopoietic cells to increase the burden of endogenous DNA damage and thereby senescence^5-7 in the immune system only. We show that Vav-iCre^+/-;Ercc1^-/fl mice were healthy into adulthood, then displayed premature onset of immunosenescence characterized by attrition and senescence of specific immune cell populations and impaired immune function, similar to changes that occur during ageing in wild-type mice^8-10. Notably, non-lymphoid organs also showed increased senescence and damage, which suggests that senescent, aged immune cells can promote systemic ageing. The transplantation of splenocytes from Vav-iCre^+/-;Ercc1^-/fl or aged wild-type mice into young mice induced senescence in trans, whereas the transplantation of young immune cells attenuated senescence. The treatment of Vav-iCre^+/-;Ercc1^-/fl mice with rapamycin reduced markers of senescence in immune cells and improved immune function^11,12. These data demonstrate that an aged, senescent immune system has a causal role in driving systemic ageing and therefore represents a key therapeutic target to extend healthy ageing.

SUBMITTER: Yousefzadeh MJ

PROVIDER: S-EPMC8684299 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Natural selection drives Drosophila immune system evolution.

Project description:Evidence from disparate sources suggests that natural selection may often play a role in the evolution of host immune system proteins. However, there have been few attempts to make general population genetic inferences on the basis of analysis of several immune-system-related genes from a single species. Here we present DNA polymorphism and divergence data from 34 genes thought to function in the innate immune system of Drosophila simulans and compare these data to those from 28 nonimmunity genes sequenced from the same lines. Several statistics, including average K(A)/K(S) ratio, average silent heterozygosity, and average haplotype diversity, significantly differ between the immunity and nonimmunity genes, suggesting an important role for directional selection in immune system protein evolution. In contrast to data from mammalian immunoglobulins and other proteins, we find no strong evidence for the selective maintenance of protein diversity in Drosophila immune system proteins. This may be a consequence of Drosophila's generalized innate immune response.

| S-EPMC1462669 | biostudies-other

Ageing and the immune system: focus on macrophages.

Project description:A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

| S-EPMC4397845 | biostudies-other

Mapping the developing human immune system across organs.

Project description:Single-cell genomics studies have decoded the immune cell composition of several human prenatal organs but were limited in describing the developing immune system as a distributed network across tissues. We profiled nine prenatal tissues combining single-cell RNA sequencing, antigen-receptor sequencing, and spatial transcriptomics to reconstruct the developing human immune system. This revealed the late acquisition of immune-effector functions by myeloid and lymphoid cell subsets and the maturation of monocytes and T cells before peripheral tissue seeding. Moreover, we uncovered system-wide blood and immune cell development beyond primary hematopoietic organs, characterized human prenatal B1 cells, and shed light on the origin of unconventional T cells. Our atlas provides both valuable data resources and biological insights that will facilitate cell engineering, regenerative medicine, and disease understanding.

| S-EPMC7612819 | biostudies-literature

Mapping the developing human immune system across organs - VDJ-seq

Project description:We profiled hematopoietic, lymphoid and peripheral fetal organs to systematically assess the heterogeneity of antigen receptors in immune cell populations across human tissues during development. Single-cell suspensions were obtained from fresh tissue. Cells were either DAPI-CD45+ or DAPI-CD45- FACS-isolated cells, or unsorted.

2022-09-23 | E-MTAB-11388 | biostudies-arrayexpress

Mapping the developing human immune system across organs - scRNA-seq

Project description:We profiled hematopoietic, lymphoid and peripheral fetal organs to systematically assess the heterogeneity of immune cell populations across human tissues during development. Single-cell suspensions were obtained from fresh tissue. Cells were either DAPI-CD45+ or DAPI-CD45- FACS-isolated cells, or unsorted.

2022-05-12 | E-MTAB-11343 | biostudies-arrayexpress

Different responses to DNA damage determine ageing differences between organs.

Project description:Organs age differently, causing wide heterogeneity in multimorbidity, but underlying mechanisms are largely elusive. To investigate the basis of organ-specific ageing, we utilized progeroid repair-deficient Ercc1Δ /- mouse mutants and systematically compared at the tissue, stem cell and organoid level two organs representing ageing extremes. Ercc1Δ /- intestine shows hardly any accelerated ageing. Nevertheless, we found apoptosis and reduced numbers of intestinal stem cells (ISCs), but cell loss appears compensated by over-proliferation. ISCs retain their organoid-forming capacity, but organoids perform poorly in culture, compared with WT. Conversely, liver ages dramatically, even causing early death in Ercc1-KO mice. Apoptosis, p21, polyploidization and proliferation of various (stem) cells were prominently elevated in Ercc1Δ /- liver and stem cell populations were either largely unaffected (Sox9+), or expanding (Lgr5+), but were functionally exhausted in organoid formation and development in vitro. Paradoxically, while intestine displays less ageing, repair in WT ISCs appears inferior to liver as shown by enhanced sensitivity to various DNA-damaging agents, and lower lesion removal. Our findings reveal organ-specific anti-ageing strategies. Intestine, with short lifespan limiting time for damage accumulation and repair, favours apoptosis of damaged cells relying on ISC plasticity. Liver with low renewal rates depends more on repair pathways specifically protecting the transcribed compartment of the genome to promote sustained functionality and cell preservation. As shown before, the hematopoietic system with intermediate self-renewal mainly invokes replication-linked mechanisms, apoptosis and senescence. Hence, organs employ different genome maintenance strategies, explaining heterogeneity in organ ageing and the segmental nature of DNA-repair-deficient progerias.

| S-EPMC9009128 | biostudies-literature

Exercise-induced immune system response: Anti-inflammatory status on peripheral and central organs.

Project description:A wide array of molecular pathways has been investigated during the past decade in order to understand the mechanisms by which the practice of physical exercise promotes neuroprotection and reduces the risk of developing communicable and non-communicable chronic diseases. While a single session of physical exercise may represent a challenge for cell homeostasis, repeated physical exercise sessions will improve immunosurveillance and immunocompetence. Additionally, immune cells from the central nervous system will acquire an anti-inflammatory phenotype, protecting central functions from age-induced cognitive decline. This review highlights the exercise-induced anti-inflammatory effect on the prevention or treatment of common chronic clinical and experimental settings. It also suggests the use of pterins in biological fluids as sensitive biomarkers to follow the anti-inflammatory effect of physical exercise.

| S-EPMC7188661 | biostudies-literature

Androgen receptor drives cellular senescence.

Project description:The accepted androgen receptor (AR) role is to promote proliferation and survival of prostate epithelium and thus prostate cancer progression. While growth-inhibitory, tumor-suppressive AR effects have also been documented, the underlying mechanisms are poorly understood. Here, we for the first time link AR anti-cancer action with cell senescence in vitro and in vivo. First, AR-driven senescence was p53-independent. Instead, AR induced p21, which subsequently reduced ?N isoform of p63. Second, AR activation increased reactive oxygen species (ROS) and thereby suppressed Rb phosphorylation. Both pathways were critical for senescence as was proven by p21 and Rb knock-down and by quenching ROS with N-Acetyl cysteine and p63 silencing also mimicked AR-induced senescence. The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation. All these pathways contributed to growth arrest, which resolved in senescence due to concomitant lack of p53 and high mTOR activity. This is the first demonstration of senescence response caused by a nuclear hormone receptor.

| S-EPMC3293868 | biostudies-literature

Cellular senescence is a double-edged sword in regulating aged immune responses to influenza.

Project description:Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective clearance of p16-expressing cells upon administration of ganciclovir (GCV). While p16-expressing cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although clearance of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV-treated mice. Furthermore, GCV-treated mice were unable to mount an optimal memory response and demonstrated increased viral load following heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.

| S-EPMC11258475 | biostudies-literature

scRNA-seq analysis of aged immune system in mice

Project description:Aging is associated with systemic chronic inflammation (inflammaging) that leads to impaired physiological functions and vulnerability to several diseases. However, underlying alterations in aged immune system resulting in gradual loss of immune fitness4 remain unclear. Using a combination of single-cell RNA/TCR/BCR-sequencing and extensive FACS/CyTOF-based validation, we comprehensively characterize age-associated alterations in immune cells in 4 mouse organs and human blood. We identified both organ-specific and common changes in immune cell populations and their transcriptional programs and found age-associated subpopulation of CD8+ T cells marked with expression of GZMK.

2020-12-06 | GSE145562 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data