dc.creator | Noren Hooten, Nicole | es |
dc.creator | Martín Montalvo, Alejandro | es |
dc.creator | Dluzen, Douglas F. | es |
dc.creator | Zhang, Yongqing | es |
dc.creator | Bernier, Michel | es |
dc.creator | Zonderman, Alan B. | es |
dc.creator | Becker, Kevin G. | es |
dc.creator | Gorospe, Myriam | es |
dc.creator | Cabo, Rafael de | es |
dc.date.accessioned | 2019-01-18T12:42:19Z | |
dc.date.available | 2019-01-18T12:42:19Z | |
dc.date.issued | 2016 | |
dc.identifier.citation | Noren Hooten, N., Martín Montalvo, A., Dluzen, D.F., Zhang, Y., Bernier, M., Zonderman, A.B.,...,Cabo, R.d. (2016). Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence. Aging Cell, 15, 572-581. | |
dc.identifier.issn | 1474-9718 (impreso) | es |
dc.identifier.issn | 1474-9726 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/81736 | |
dc.description.abstract | Metformin, an oral hypoglycemic agent, has been used for
decades to treat type 2 diabetes mellitus. Recent studies indicate
that mice treated with metformin live longer and have fewer
manifestations of age-related chronic disease. However, the
molecular mechanisms underlying this phenotype are unknown.
Here, we show that metformin treatment increases the levels of
the microRNA-processing protein DICER1 in mice and in humans
with diabetes mellitus. Our results indicate that metformin
upregulates DICER1 through a post-transcriptional mechanism
involving the RNA-binding protein AUF1. Treatment with metformin
altered the subcellular localization of AUF1, disrupting its
interaction with DICER1 mRNA and rendering DICER1 mRNA
stable, allowing DICER1 to accumulate. Consistent with the role
of DICER1 in the biogenesis of microRNAs, we found differential
patterns of microRNA expression in mice treated with metformin
or caloric restriction, two proven life-extending interventions.
Interestingly, several microRNAs previously associated with
senescence and aging, including miR-20a, miR-34a, miR-130a,
miR-106b, miR-125, and let-7c, were found elevated. In agreement
with these findings, treatment with metformin decreased
cellular senescence in several senescence models in a DICER1-
dependent manner. Metformin lowered p16 and p21 protein
levels and the abundance of inflammatory cytokines and oncogenes
that are hallmarks of the senescence-associated secretory
phenotype (SASP). These data lead us to hypothesize that
changes in DICER1 levels may be important for organismal aging
and to propose that interventions that upregulate DICER1
expression (e.g., metformin) may offer new pharmacotherapeutic
approaches for age-related disease. | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Anatomical Society of Great Britain and Ireland, John Wiley & Sons | es |
dc.relation.ispartof | Aging Cell, 15, 572-581. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Aging | es |
dc.subject | AUF1 | es |
dc.subject | Caloric restriction | es |
dc.subject | Diabetes mellitus | es |
dc.subject | MicroRNA | es |
dc.subject | RNA-binding proteins | es |
dc.title | Metformin-mediated increase in DICER1 regulates microRNA expression and cellular senescence | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/acceptedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.relation.publisherversion | http://dx.doi.org/10.1111/acel.12469 | es |
dc.identifier.doi | 10.1111/acel.12469 | es |
idus.format.extent | 10 p. | es |
dc.journaltitle | Aging Cell | es |
dc.publication.volumen | 15 | es |
dc.publication.initialPage | 572 | es |
dc.publication.endPage | 581 | es |