LySR, a lysosomal surveillance response that extends healthspan [Exp1]
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ABSTRACT:
PROVIDER: PRJNA803027 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Lysosomes are cytoplasmic organelles that are central for the degradation of macromolecules to maintain cellular homeostasis and health. Here, we discovered an adaptive lysosomal transcriptional response that we termed the lysosomal stress response (LySR). Typified by the induction of a large group of transcripts involved in lysosomal function and proteolysis, the LySR can be triggered by silencing of specific vacuolar H+-ATPase subunits in Caenorhabditis elegans. Notably, LySR activation enhances the clearance of protein aggregates in worm models of Alzheimer's and Huntington’s disease and amyotrophic lateral sclerosis, thereby boosting fitness and extending lifespan, a response that is controlled by the GATA transcription factor, ELT-2. Activating the LySR pathway may therefore represent an attractive mechanism to reduce protein aggregation and, as such, extend healthspan.
2023-02-03 | GSE196021 | GEO
Project description:LySR, a lysosomal surveillance response that extends healthspan [Exp2]
| PRJNA803034 | ENA
Project description:Lysosomes are cytoplasmic organelles that are central for the degradation of macromolecules to maintain cellular homeostasis and health. Here, we discovered an adaptive lysosomal transcriptional response that we termed the lysosomal stress response (LySR). Typified by the induction of a large group of transcripts involved in lysosomal function and proteolysis, the LySR can be triggered by silencing of specific vacuolar H+-ATPase subunits in Caenorhabditis elegans. Notably, LySR activation enhances the clearance of protein aggregates in worm models of Alzheimer's and Huntington’s disease and amyotrophic lateral sclerosis, thereby boosting fitness and extending lifespan, a response that is controlled by the GATA transcription factor, ELT-2. Activating the LySR pathway may therefore represent an attractive mechanism to reduce protein aggregation and, as such, extend healthspan.
2023-02-03 | GSE196022 | GEO
Project description:A lysosomal surveillance response that extends healthspan
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Project description:Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice
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Project description:This SuperSeries is composed of the SubSeries listed below.
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Project description:Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of increased HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exploited to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan
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