MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. Export

@article{citeulike:6066137, abstract = {SUMMARY The Ames dwarf mouse is well known for its remarkable propensity to delay the onset of aging. Although significant advances have been made demonstrating that this aging phenotype results primarily from an endocrine imbalance, the posttranscriptional regulation of gene expression and its impact on longevity remains to be explored. Towards this end, we present the first comprehensive study by microRNA microarray screening to identify dwarf-specific lead microRNAs, and investigate their roles as pivotal molecular regulators directing the long-lived phenotype. Mapping the signature microRNAs to the inversely expressed putative target genes, followed by in situ immunohistochemical staining and in vitro correlation assays, reveal that dwarf mice posttranscriptionally regulate key proteins of intermediate metabolism, most importantly the biosynthetic pathway involving ornithine decarboxylase and spermidine synthase. Functional assays using 3'UTR reporter constructs in co-transfection experiments confirm that microRNA-27a indeed suppresses the expression of both of these proteins, marking them as probable targets of this microRNA in vivo. Moreover, the putative repressed action of this microRNA on ornithine decarboxylase is identified in dwarf mouse liver as early as two months of age. Taken together, our results show that among the altered aspects of intermediate metabolism detected in the dwarf mouse liver - glutathione metabolism, the urea cycle, and polyamine biosynthesis -microRNA-27a is a key posttranscriptional control. Furthermore, compared to its normal siblings, the dwarf mouse exhibits a head start in regulating these pathways to control their normality, which may ultimately contribute to its extended healthspan and longevity.}, author = {Bates, David J. and Li, Na and Liang, Ruqiang and Sarojini, Harshini and An, Jin and Masternak, Michal M. and Bartke, Andrzej and Wang, Eugenia}, citeulike-article-id = {6066137}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1474-9726.2009.00529.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19878148}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19878148}, day = {30}, doi = {10.1111/j.1474-9726.2009.00529.x}, issn = {1474-9726}, journal = {Aging cell}, keywords = {aging, function, mirna, regulation}, month = {October}, posted-at = {2009-11-04 01:43:56}, priority = {2}, title = {MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging.}, url = {http://dx.doi.org/10.1111/j.1474-9726.2009.00529.x}, year = {2009} }

TY - JOUR ID - citeulike:6066137 L3 - citeulike-article-id:6066137 N2 - SUMMARY The Ames dwarf mouse is well known for its remarkable propensity to delay the onset of aging. Although significant advances have been made demonstrating that this aging phenotype results primarily from an endocrine imbalance, the posttranscriptional regulation of gene expression and its impact on longevity remains to be explored. Towards this end, we present the first comprehensive study by microRNA microarray screening to identify dwarf-specific lead microRNAs, and investigate their roles as pivotal molecular regulators directing the long-lived phenotype. Mapping the signature microRNAs to the inversely expressed putative target genes, followed by in situ immunohistochemical staining and in vitro correlation assays, reveal that dwarf mice posttranscriptionally regulate key proteins of intermediate metabolism, most importantly the biosynthetic pathway involving ornithine decarboxylase and spermidine synthase. Functional assays using 3'UTR reporter constructs in co-transfection experiments confirm that microRNA-27a indeed suppresses the expression of both of these proteins, marking them as probable targets of this microRNA in vivo. Moreover, the putative repressed action of this microRNA on ornithine decarboxylase is identified in dwarf mouse liver as early as two months of age. Taken together, our results show that among the altered aspects of intermediate metabolism detected in the dwarf mouse liver - glutathione metabolism, the urea cycle, and polyamine biosynthesis -microRNA-27a is a key posttranscriptional control. Furthermore, compared to its normal siblings, the dwarf mouse exhibits a head start in regulating these pathways to control their normality, which may ultimately contribute to its extended healthspan and longevity. JF - Aging cell SN - 1474-9726 TI - MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. KW - aging KW - function KW - mirna KW - regulation AU - Bates, David AU - Li, Na AU - Liang, Ruqiang AU - Sarojini, Harshini AU - An, Jin AU - Masternak, Michal AU - Bartke, Andrzej AU - Wang, Eugenia PY - 2009/10/30/ UR - http://dx.doi.org/10.1111/j.1474-9726.2009.00529.x ER -