Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Senescent glia link neuronal mitochondrial dysfunction and lipid droplet accumulation with age [19082-12_MASTER]

ABSTRACT: Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE263927 | GEO | 2024/05/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Senescent glia link neuronal mitochondrial dysfunction and lipid droplet accumulation with age

Project description:Senescence is a cellular state linked to aging and age-onset disease across many mammalian species. Acutely, senescent cells promote wound healing and prevent tumor formation; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. While senescent cells are active targets for anti-aging therapy, why these cells form in vivo, how they affect tissue aging, and the impact of their elimination remain unclear. Here we identify naturally-occurring senescent glia in aged Drosophila brains and decipher their origin and influence. Using AP1 activity to screen for senescence, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly life and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally-occurring senescent glia in vivo and indicate that these cells link key aging phenomena: mitochondrial dysfunction and lipid accumulation.

2024-05-24 | GSE263928 | GEO

Senescent glia link neuronal mitochondrial dysfunction and lipid droplet accumulation with age [19082R-38_MASTER]

2024-05-24 | GSE263926 | GEO

Senescent glia link neuronal mitochondrial dysfunction and lipid droplet accumulation with age [19082_28_MASTER]

2024-05-24 | GSE263929 | GEO

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

Project description:The accumulation of irreparable cellular damage restricts healthy lifespan after acute stress or natural aging. Senescent cells are thought to impair tissue function and their genetic clearance can successfully delay features of aging. Identifying how senescent cells avoid apoptosis would allow for the prospective design of anti-senescence compounds to address whether homeostasis can be restored. Here, we identify FOXO4 as a pivot in the maintenance of senescent cell viability. We designed a FOXO4-based peptide which selectively competes for interaction of FOXO4 with p53. In senescent cells, this results in p53 nuclear exclusion and cell-intrinsic apoptosis. Importantly, under conditions where it was well tolerated, the FOXO4 peptide restored liver function after Doxorubicin-induced chemotoxicity. Moreover, in fast aging XpdTTD/TTD, as well as in naturally aged mice the FOXO4 peptide could counteract the loss of fitness, fur density and renal function. Thus, it is possible to therapeutically target senescent cells and thereby effectively counteract senescence-associated loss of tissue homeostasis.

2017-03-01 | GSE94395 | GEO

Transcriptomic landscape of mouse pulmonary alveolar cells upon chronological aging and/or anti-senescence intervention

Project description:As a critical hallmark of senescent cells, the senescence-associated secretory phenotype (SASP) develops over the course of chronological aging and in diverse age-related conditions, and is a key driver of chronic inflammation and age-associated phenotypes. For years, the identification, characterization and pharmacological targeting of senescent cells have gained substantial attention in the field of aging and age-related pathologies. Pyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy regulation, and drives the metabolic reprogramming of mammalian cells towards a Warburg-like effect. Upregulation of PDK4 is responsible for enhanced production of lactate in the tissue microenvironment of aged organisms, potentially causing chronic inflammation and contributing to accelerated aging. Targeting PDK4 holds the potential to prevent lactate accumulation, minimize tissue damage and postpone senescence-associated systemic aging. Here we profiled the genome-wide expression of cells (mainly fibroblasts) in mouse pulmonary alveolus, with the assistance of laser capture microdissection (LCM) of primary lung tissues. Animals were allowed to naturally age, or subject to treatment by PDK4-IN (an anthraquinone derivative, PDK4 inhibitor). These data may provide a baseline to further determine the effects of lactate reduction by PDK4-specific targeting on cellular senescence, tissue homeostasis, and explore the wide implications of PDK4 expression in organismal aging and age-related morbidity.

2023-09-05 | GSE217808 | GEO

Characterization of premature cell senescence in Alzheimer’s disease using single nuclear transcriptomics

Project description:Aging is associated with cell senescence and is the major risk factor for AD. We characterized premature cell senescence in post mortem brains from non-diseased controls (NDC) and donors with Alzheimer’s disease (AD) using imaging mass cytometry (IMC) and single nuclear RNA (snRNA) sequencing (>200,000 nuclei). We found increases in numbers of glia immunostaining for galactosidase beta (>4-fold) and p16INK4A (up to 2-fold) with AD relative to NDC. Increased glial expression of genes related to senescence was associated with greater -amyloid load. Prematurely senescent microglia downregulated phagocytic pathways suggesting reduced capacity for -amyloid clearance. Gene set enrichment and pseudo-time trajectories described extensive DNA double-strand breaks (DSBs), mitochondrial dysfunction and ER stress associated with increased β-amyloid leading to premature senescence in microglia. We replicated these observations with independent AD snRNA-seq datasets. Our results describe a burden of senescent glia with AD that is sufficiently high to contribute to disease progression. These findings support the hypothesis that microglia are a primary target for senolytic treatments in AD.

2024-04-26 | GSE264648 | GEO

Naked mole rat cells are protected from cellular senescence via Wnt/β-catenin-promoted cholesterol metabolism

Project description:The naked mole rat (NMR; Heterocephalus glaber) exhibits cancer resistance and an exceptionally long lifespan of approximately 30 years. The longevity of the NMR is widely debated, as it poses challenges to theories associated with aging, cancer, and redox homeostasis. In the present study, we report unique mechanisms of cholesterol metabolism in NMR cells that could be responsible in part for their anti-senescent properties. We found that NMR fibroblasts abundantly express β-catenin, and that increased β-catenin activity is linked to increased accumulation of cholesterol-enriched lipid droplets. Either β-catenin knockdown or inhibition of cholesterol synthesis abolished lipid droplet formation, and enhanced induction of senescence-like phenotypes. Analysis of β-catenin-regulated genes revealed that β-catenin upregulated the LXR/RXR pathway and Apolipoprotein F, which are involved in cholesterol biogenesis and transport. Specifically, Apolipoprotein F is involved in the accumulation of lipid droplets, protecting NMR cells from cellular senescence. We thus suggest that increased β-catenin activity evolved in NMRs to offset senescence via the accumulation of cholesterol-enriched lipid droplets. Hence, the anti-senescence effects of the Wnt/β-catenin signaling in NMRs reveals new strategies for the development of anti-cancer and anti-aging treatments.

2021-02-21 | GSE147871 | GEO

Age-associated decline of MondoA drives cellular senescence through impaired autophagy and mitochondrial homeostasis

Project description:Accumulation of senescent cells affects organismal aging and the prevalence of age-associated disease. Emerging evidence suggests that activation of autophagy protects against age-associated diseases and promotes longevity, but the roles and regulatory mechanisms of autophagy in cellular senescence are not well understood. Here we identified the transcription factor, MondoA, as a novel regulator of cellular senescence, autophagy and mitochondrial homeostasis. MondoA protected against cellular senescence by activating autophagy partly through the suppression of an autophagy negative regulator, Rubicon. In addition, we identified peroxiredoxin 3 (Prdx3) as another downstream regulator of MondoA essential for mitochondrial homeostasis and autophagy. Rubicon and Prdx3 worked independently to regulate senescence. Furthermore, we found that MondoA knockout mice had exacerbated senescence during ischemic acute kidney injury (AKI), and a decrease of MondoA in the nucleus was correlated with human aging and ischemic AKI. Our results suggest that retaining MondoA activity protects from senescence and age-associated disease.

2022-03-01 | GSE179016 | GEO

Micro bulk sequencing on murine Bleomycin-induced fibrotic lungs sorted on SA-β-Gal and GD3

Project description:Aging is marked by a progressive decline in physiological function, leading to an increased susceptibility to age-related diseases and cancer. On the cellular level, aging correlates with an accumulation of senescent cells, which play a dual role: they are critical for tissue homeostasis, yet their over-accumulation may drive pathological aging. We recently revealed that senescent cells could overexpress immunosuppressive molecules like the ganglioside GD3 at their cell surface to evade from immune surveillance and to facilitate their tolerogenicity. We investigate which cells expressed GD3 and whether this ganglioside could be considered as a new marker associated to senescence in a model of senescence associated disease: Bleomycin-induced lung fibrosis.

2024-04-04 | GSE262926 | GEO

Regulation of Lipids is Central to Replicative Senescence

Project description:Cellular replicative senescence, a state of permanent cell-cycle arrest that occurs following an extended period of cell division in culture, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblast cells. We found that both the expression levels of lipid-regulating genes, as well as the abundance of specific lipid families, are actively regulated. We further found that 19 polyunsaturated triacylglycerol species showed the most prominent changes during replicative senescence. We argue that diversion of polyunsaturated fatty acids to glycerolipid biosynthesis could be responsible for the accumulation of specific triacylglycerols. This, in turn, could be one of the cellular mechanisms to prevent lipotoxicity under increased oxidative stress conditions observed during replicative senescence. Collectively, our results place regulation of specific lipid species to a central role during replicative senescence.

2017-03-31 | GSE94280 | 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