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A lysosomal surveillance response (LySR) that boosts lysosomal activity and extends healthspan [Exp1]

ABSTRACT: A lysosomal surveillance response (LySR) that boosts lysosomal activity and 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 (LySR) that boosts lysosomal activity and 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 featured by boosted lysosomal activity, enhanced clearance of protein aggregates in worm models of Alzheimer's and 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 (LySR) that boosts lysosomal activity and extends healthspan [Exp2]

2023-02-03 | GSE196022 | GEO

A lysosomal surveillance response (LySR) that boosts lysosomal activity and extends healthspan

Project description:A lysosomal surveillance response (LySR) that boosts lysosomal activity and extends healthspan

| PRJNA803026 | ENA

A lysosomal surveillance response (LySR) that boosts lysosomal activity and extends healthspan [Exp2]

Project description:A lysosomal surveillance response (LySR) that boosts lysosomal activity and extends healthspan [Exp2]

| PRJNA803034 | ENA

A lysosomal surveillance response (LySR) that boosts lysosomal activity and 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: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

2023-09-08 | GSE234154 | GEO

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

2023-08-10 | GSE234563 | GEO

Evolutionarily-conserved FOXO-regulated OSER1 extends lifespan and healthspan

Project description:Molecular aging reflects the time-dependent accumulation of cellular damage and loss of essential cellular functions. FOXO transcription factors and their downstream targets play critical roles in the response to aging-associated cellular damage. Here, we identify and characterize a novel FOXO-regulated stress response gene, Oxidative Stress Responsive Serine-rich Protein 1 (OSER1), whose level of expression dramatically influences lifespan in Bombyx mori, Caenorhabditis elegans, and Drosophila. Overexpression of OSER1 also enhances resistance to oxidative stress, starvation, and heat shock, whereas depletion increases susceptibility to these stressors. In humans, common OSER1 genetic variants are associated with longevity. These data show that OSER1 modulates the oxidative stress response and suggest that OSER1 is a potent positive regulator of lifespan and healthspan in multiple species.

2024-07-25 | PXD036579 | Pride

18S metagenome exp1

Project description:18S metagenome exp1 Raw sequence reads

| PRJNA550445 | ENA

Systemic lipolysis promotes healthspan in Drosophila melanogaster

Project description:Since healthspan-extending interventions such as caloric restriction or fasting robustly promote lipid catabolism, we investigated how lifespan and healthspan were affected by increased lipid catabolism via bmm (brummer, FBgn0036449), the major triglyceride hydrolase in Drosophila. Global overexpression of bmm strongly promoted lifespan extension as well as numerous markers of healthspan, including increased female fecundity, fertility maintenance, preserved locomotion activity, increased mitochondrial biogenesis and oxidative metabolism. Increased Bmm robustly upregulated the heat shock protein 70 (Hsp70) family of proteins, which equipped the flies with higher resistance to heat, cold, and ER stress via improved proteostasis. Overexpression of bmm recapitulated major physiological changes associated with dietary restriction (DR) and conveyed its effects through dSir2. Taken together, these data show that bmm overexpression has broad beneficial effects on healthspan, and implicate lipolysis as a key node underlying the beneficial effects of dietary interventions known to improve healthspan.

2022-09-27 | GSE178816 | GEO

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