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The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan

ABSTRACT: The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan

PROVIDER: PRJNA1219486 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32236800_1.fastq.gz	Fastqsanger.gz
	SRR32236800_2.fastq.gz	Fastqsanger.gz
	SRR32236900_1.fastq.gz	Fastqsanger.gz
	SRR32236900_2.fastq.gz	Fastqsanger.gz
	SRR32236801_1.fastq.gz	Fastqsanger.gz

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The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan

Project description:Suppression of the insulin/IGF/mTORC1/Ras network ameliorates ageing in animals. Many drugs have targets in the network because of its roles in cancer and metabolic disease, and are candidates for repurposing as geroprotectors. Rapamycin, an established geroprotective drug, blocks mTORC1 signalling while trametinib inhibits the Ras/MEK/ERK pathway. We assessed survival and health of male and female mice treated with trametinib, rapamycin or their combination. Here we show, that trametinib treatment extended lifespan in both sexes and its combination with rapamycin caused additive prolongation. Combination-treatment reduced liver tumours in both sexes and spleen tumours in males, blocked the age-related increase in brain glucose uptake, and strongly reduced inflammation in brain, kidney, spleen and muscle and circulating levels of pro-inflammatory cytokines. Trametinib, which had no obvious side-effects, is therefore geroprotective in mice, and its combination with rapamycin is more effective than either drug alone, making it a candidate for repurposing as a geroprotector in humans.

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