{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zhang J"],"funding":["National Natural Science Foundation of China","China Postdoctoral Science Foundation","National Key Research and Development Program of China"],"pagination":["e475"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10924637"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(3)"],"pubmed_abstract":["Senescence-associated microRNAs (SA-miRNAs) are important molecules for aging regulation. While many aging-promoting SA-miRNAs have been identified, confirmed aging-suppressive SA-miRNAs are rare, that impeded our full understanding on aging regulation. In this study, we verified that miR-708 expression is decreased in senescent cells and aged tissues and revealed that miR-708 overexpression can alleviate cellular senescence and aging performance. About the molecular cascade carrying the aging suppressive action of miR-708, we unraveled that miR-708 directly targets the 3'UTR of the disabled 2 (<i>Dab2</i>) gene and inhibits the expression of DAB2. Interestingly, miR-708-caused DAB2 downregulation blocks the aberrant mammalian target of rapamycin complex 1 (mTORC1) activation, a driving metabolic event for senescence progression, and restores the impaired autophagy, a downstream event of aberrant mTORC1 activation. We also found that AMP-activated protein kinase (AMPK) activation can upregulate miR-708 via the elevation of DICER expression, and miR-708 inhibitor is able to blunt the antiaging effect of AMPK. In summary, this study characterized miR-708 as an aging-suppressive SA-miRNA for the first time and uncovered a new signaling cascade, in which miR-708 links the DAB2/mTOR axis and AMPK/DICER axis together. These findings not only demonstrate the potential role of miR-708 in aging regulation, but also expand the signaling network connecting AMPK and mTORC1."],"journal":["MedComm"],"pubmed_title":["AMPK-upregulated microRNA-708 plays as a suppressor of cellular senescence and aging via downregulating disabled-2 and mTORC1 activation."],"pmcid":["PMC10924637"],"funding_grant_id":["2018YFC2000400","82071589,82101629","2022M722282"],"pubmed_authors":["Liu J","Zhang J","Yang M","Huang N","Wang F","Zhao T","Chen H","Yang Y","Gong C","Li T","Xiao H","Zhang C","Xu W","Gong H"],"additional_accession":[]},"is_claimable":false,"name":"AMPK-upregulated microRNA-708 plays as a suppressor of cellular senescence and aging via downregulating disabled-2 and mTORC1 activation.","description":"Senescence-associated microRNAs (SA-miRNAs) are important molecules for aging regulation. While many aging-promoting SA-miRNAs have been identified, confirmed aging-suppressive SA-miRNAs are rare, that impeded our full understanding on aging regulation. In this study, we verified that miR-708 expression is decreased in senescent cells and aged tissues and revealed that miR-708 overexpression can alleviate cellular senescence and aging performance. About the molecular cascade carrying the aging suppressive action of miR-708, we unraveled that miR-708 directly targets the 3'UTR of the disabled 2 (<i>Dab2</i>) gene and inhibits the expression of DAB2. Interestingly, miR-708-caused DAB2 downregulation blocks the aberrant mammalian target of rapamycin complex 1 (mTORC1) activation, a driving metabolic event for senescence progression, and restores the impaired autophagy, a downstream event of aberrant mTORC1 activation. We also found that AMP-activated protein kinase (AMPK) activation can upregulate miR-708 via the elevation of DICER expression, and miR-708 inhibitor is able to blunt the antiaging effect of AMPK. In summary, this study characterized miR-708 as an aging-suppressive SA-miRNA for the first time and uncovered a new signaling cascade, in which miR-708 links the DAB2/mTOR axis and AMPK/DICER axis together. These findings not only demonstrate the potential role of miR-708 in aging regulation, but also expand the signaling network connecting AMPK and mTORC1.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-06T01:55:45.976Z","creation":"2025-04-04T12:58:48.636Z"},"accession":"S-EPMC10924637","cross_references":{"pubmed":["38463393"],"doi":["10.1002/mco2.475"]}}