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Epigenetic aging of the demographically non-aging naked mole-rat [RRBS]

ABSTRACT: Epigenetic aging of the demographically non-aging naked mole-rat [RRBS]

PROVIDER: PRJNA742002 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14930600_1.fastq.gz	Fastqsanger.gz
	SRR14930600_2.fastq.gz	Fastqsanger.gz
	SRR14930601_1.fastq.gz	Fastqsanger.gz
	SRR14930601_2.fastq.gz	Fastqsanger.gz
	SRR14930602_1.fastq.gz	Fastqsanger.gz

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Epigenetic aging of the demographically non-aging naked mole-rat [RRBS]

Project description:The naked mole-rat (NMR) is an exceptionally long-lived rodent that does not show increased mortality with age, uniquely defining NMR as a demographically non-aging mammal. Here, we performed bisulfite sequencing on over one hundred NMR blood samples differing in age, assessing more than 3 million common CpG sites. We observed an information loss of the NMR methylome during aging suggesting that NMR ages. Unsupervised clustering based on the 758 CpG sites whose methylation level strongly correlate with age suggests an age-related shift of the NMR methylome. We also developed an epigenetic aging clock that accurately predicts the NMR age spread across the genome. Based on the clock, NMRs age much slower than mice and much faster than humans, consistent with their known maximum lifespans. We further found that patterns of age-related methylation changes of aging clock sites in Tert and Prpf19 showed differences between NMRs and mice. Together, the data indicate that NMRs, like other mammals, epigenetically age even in the absence of demographic aging of this species.

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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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