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A lysosomal surveillance response to stress extends healthspan [Exp1]

ABSTRACT: A lysosomal surveillance response to stress extends healthspan [Exp1]

PROVIDER: PRJNA803027 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17868968.fastq.gz	Fastqsanger.gz
	SRR17868969.fastq.gz	Fastqsanger.gz
	SRR17868970.fastq.gz	Fastqsanger.gz
	SRR17868971.fastq.gz	Fastqsanger.gz
	SRR17868972.fastq.gz	Fastqsanger.gz

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A lysosomal surveillance response to stress extends healthspan [Exp1]

Project description:Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homeostasis and health. However, how lysosomal activity can be boosted to counteract aging and aging-related diseases remains elusive. Here, we reveal that silencing specific vacuolar H+-ATPase subunits (e.g. vha-6), that are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive transcriptional response typified by induction of a set of transcripts involved in lysosomal function and proteolysis, which we termed the lysosomal surveillance response (LySR). LySR activation is characterized by boosted lysosomal activity, enhanced clearance of protein aggregates in worm models of Alzheimer's disease, Huntington’s disease and amyotrophic lateral sclerosis, thereby improving fitness. The GATA transcription factor ELT-2 governs the LySR program and its associated beneficial effects. Activating the LySR pathway may therefore represent an attractive mechanism to reduce proteotoxicity and, as such, potentially extend healthspan.

2023-02-03 | GSE196021 | GEO

A lysosomal surveillance response to stress extends healthspan

Project description:A lysosomal surveillance response to stress extends healthspan

| PRJNA803026 | ENA

A lysosomal surveillance response to stress extends healthspan [Exp3]

Project description:A lysosomal surveillance response to stress extends healthspan [Exp3]

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A lysosomal surveillance response to stress extends healthspan [Exp2]

Project description:A lysosomal surveillance response to stress extends healthspan [Exp2]

| PRJNA803034 | ENA

A lysosomal surveillance response to stress extends healthspan [Exp2]

2023-02-03 | GSE196022 | GEO

A lysosomal surveillance response to stress extends healthspan [Exp3]

2025-05-03 | GSE296199 | GEO

A lysosomal surveillance response to stress extends healthspan

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-02-03 | GSE196023 | GEO

Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

Project description:Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

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Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

Project description:Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

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Increased hyaluronan by naked mole-rat HAS2 extends healthspan in mice

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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