{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T13:13:33Z","timestamp":1782998013126,"version":"3.54.5"},"reference-count":93,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1403\/14"],"award-info":[{"award-number":["1403\/14"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The growth hormone (GH)\u2013insulin-like growth factor-1 (IGF1) endocrine axis is a central player in normal growth and metabolism as well as in a number of pathologies, including cancer. The GH\u2013IGF1 hormonal system, in addition, has emerged as a major determinant of lifespan and healthspan. Laron syndrome (LS), the best characterized entity under the spectrum of the congenital IGF1 deficiencies, results from mutation of the GH receptor (GHR) gene, leading to dwarfism, obesity and other defects. Consistent with the key role of IGF1 in cellular proliferation, epidemiological studies have shown that LS patients are protected from cancer development. While reduced expression of components of the GH-IGF1 axis is associated with enhanced longevity in animal models, it is still unknown whether LS is associated with an increased lifespan. MicroRNAs (miRs) are endogenous short non-coding RNAs that regulate the expression of complementary mRNAs. While a number of miRs involved in the regulation of IGF components have been identified, no previous studies have investigated the differential expression of miRs in congenital IGF1 deficiencies. The present study was aimed at identifying miRs that are differentially expressed in LS and that might account for the phenotypic features of LS patients, including longevity. Our genomic analyses provide evidence that miR-132-3p was highly expressed in LS. In addition, we identified SIRT1, a member of the sirtuin family of histone deacetylases, as a target for negative regulation by miR-132-3p. The data was consistent with the notion that low concentrations of IGF1 in LS lead to elevated miR-132-3p levels, with ensuing reduction in SIRT1 gene expression. The impact of the IGF1-miR-132-3p-SIRT1 loop on aging merits further investigation.<\/jats:p>","DOI":"10.3390\/ijms222111861","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:21:34Z","timestamp":1635805294000},"page":"11861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["MicroRNA 132-3p Is Upregulated in Laron Syndrome Patients and Controls Longevity Gene Expression"],"prefix":"10.3390","volume":"22","author":[{"given":"Danielle","family":"Yaron-Saminsky","sequence":"first","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Nagaraj","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rive","family":"Sarfstein","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zvi","family":"Laron","sequence":"additional","affiliation":[{"name":"Schneider Children\u2019s Medical Center, Endocrinology and Diabetes Research Unit, 49292 Petah Tikva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Metsada","family":"Pasmanik-Chor","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, The George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0154-1290","authenticated-orcid":false,"given":"Haim","family":"Werner","sequence":"additional","affiliation":[{"name":"Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ecl.2012.04.008","article-title":"Insulin-like growth factor 1 physiology: Lessons from mouse models","volume":"41","author":"Yakar","year":"2012","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/ncpendmet0427","article-title":"Mechanisms of disease: Metabolic effects of growth hormone and insulin-like growth factor-1","volume":"3","author":"LeRoith","year":"2007","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1210\/mend-4-9-1386","article-title":"Cellular pattern of insulin-like growth factor I (IGF-I) and type I IGF receptor gene expression in early organogenesis: Comparison with IGF-II gene expression","volume":"4","author":"Bondy","year":"1990","journal-title":"Mol. Endocrinol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7451","DOI":"10.1073\/pnas.86.19.7451","article-title":"Developmental regulation of the rat insulin-like growth factor I receptor gene","volume":"86","author":"Werner","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"T115","DOI":"10.1530\/JME-17-0298","article-title":"Insulin-like growth factors: Actions on the skeleton","volume":"61","author":"Yakar","year":"2018","journal-title":"J. Mol. Endocrinol"},{"key":"ref_6","first-page":"825","article-title":"A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro","volume":"49","author":"Salmon","year":"1957","journal-title":"J. Lab. Clin. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1056\/NEJMp038156","article-title":"Insulin-like growth factors and the basis of growth","volume":"349","author":"Rosenfeld","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_8","first-page":"39","article-title":"Genetic mutations in the GH\/IGF axis","volume":"16","year":"2018","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.tem.2006.08.006","article-title":"Obesity and cancer risk: The role of the insulin-IGF axis","volume":"17","author":"Renehan","year":"2006","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1126\/science.279.5350.563","article-title":"Plasma insulin-like growth factor-I and prostate cancer risk: A prospective study","volume":"279","author":"Chan","year":"1998","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/S0140-6736(97)10384-1","article-title":"Circulating concentrations of insulin-like growth factor-I and risk of breast cancer","volume":"351","author":"Hankinson","year":"1998","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1079\/PNS200070","article-title":"Energy balance and cancer: The role of insulin and insulin-like growth factors","volume":"60","author":"Kaaks","year":"2001","journal-title":"Proc. Nutr. Soc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e537","DOI":"10.1016\/S1470-2045(12)70362-5","article-title":"IGF-1 and BRCA1 signalling pathways in familial cancer","volume":"13","author":"Werner","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.mce.2006.03.018","article-title":"Transcriptional regulation of the insulin-like growth factor-1 receptor in breast cancer","volume":"252","author":"Sarfstein","year":"2006","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/nrc3215","article-title":"The insulin and insulin-like growth factor receptor family in neoplasia: An update","volume":"12","author":"Pollak","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1038\/onc.2011.447","article-title":"Tumor suppressors govern insulin-like growth factor signaling pathways: Implications in metabolism and cancer","volume":"31","author":"Werner","year":"2012","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1038\/sj.onc.1203854","article-title":"The contradictions of the insulin-like growth factor 1 receptor","volume":"19","author":"Baserga","year":"2000","journal-title":"Oncogene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ecl.2012.04.009","article-title":"Insulin-like growth factor physiology: What we have learned from human studies","volume":"41","author":"Holly","year":"2012","journal-title":"Endocrinol. Metab. Clin. North Am."},{"key":"ref_19","first-page":"739","article-title":"Clinical relevance of systemic and local IGF-I: Lessons from animal models","volume":"5","author":"LeRoith","year":"2008","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1210\/jc.2003-031033","article-title":"Extensive personal experience. Laron syndrome (primary growth hormone resistance or insensitivity): The personal experience 1958-2003","volume":"89","author":"Laron","year":"2004","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Laron, Z., and Kopchik, J.J. (2011). Laron Syndrome\u2014From Man to Mouse, Springer.","DOI":"10.1007\/978-3-642-11183-9"},{"key":"ref_22","first-page":"152","article-title":"Genetic pituitary dwarfism with high serum concentration of growth hormone-a new inborn error of metabolism?","volume":"2","author":"Laron","year":"1966","journal-title":"Isr. J. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1677\/jme.0.0100115","article-title":"Up-regulation of insulin-like growth factor-I (IGF-I) receptor gene expression in patients with reduced serum IGF-I levels","volume":"10","author":"Eshet","year":"1993","journal-title":"J. Mol. Endocrinol."},{"key":"ref_24","first-page":"489","article-title":"Genetic analysis of the pedigrees and molecular defects of the GH-receptor gene in the Israeli cohort of patients with Laron syndrome","volume":"3","author":"Shevah","year":"2006","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJM198910123211501","article-title":"Laron dwarfism and mutations of the growth hormone-receptor gene","volume":"321","author":"Amselem","year":"1989","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8083","DOI":"10.1073\/pnas.86.20.8083","article-title":"Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism","volume":"86","author":"Godowski","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ghir.2006.10.007","article-title":"Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: A preliminary report","volume":"17","author":"Shevah","year":"2007","journal-title":"Growth Horm. IGF Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1530\/EJE-10-0859","article-title":"Congenital IGF1 deficiency tends to confer protection against post-natal development of malignancies","volume":"164","author":"Steuerman","year":"2011","journal-title":"Eur. J. Endocrinol."},{"key":"ref_29","first-page":"70ra13","article-title":"Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans","volume":"3","author":"Balasubramanian","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fendo.2019.00027","article-title":"Role of IGF-1 system in the modulation of longevity: Controversies and new insights from a centenarian\u2019s perspective","volume":"10","author":"Vitale","year":"2019","journal-title":"Front. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1126\/science.277.5328.942","article-title":"daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans","volume":"277","author":"Kimura","year":"1997","journal-title":"Science"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1111\/j.1474-9726.2011.00697.x","article-title":"Impaired IGF1R signaling in cells expressing longevity-associated human IGF1R alleles","volume":"10","author":"Tazearslan","year":"2011","journal-title":"Aging Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1210\/endo.141.7.7586","article-title":"Assessment of growth parameters and life span of GHR\/BP gene-disrupted mice","volume":"141","author":"Coschigano","year":"2000","journal-title":"Endocrinology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R155","DOI":"10.1530\/EJE-18-0018","article-title":"Lessons from growth hormone receptor gene-disrupted mice: Are there benefits of endocrine defects?","volume":"178","author":"Basu","year":"2018","journal-title":"Eur. J. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0168-9525(02)02696-3","article-title":"A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan","volume":"18","author":"Carter","year":"2002","journal-title":"Trends Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mrrev.2016.08.002","article-title":"IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome","volume":"772","author":"Laron","year":"2017","journal-title":"Mutat. Res. Rev. Mutat. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1159\/000073704","article-title":"Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice","volume":"78","author":"Bartke","year":"2003","journal-title":"Neuroendocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1530\/ERC-16-0054","article-title":"Identification of signaling pathways associated with cancer protection in Laron syndrome","volume":"23","author":"Rotem","year":"2016","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1073\/pnas.1715930115","article-title":"Identification of thioredoxin-interacting protein (TXNIP) as a downstream target for IGF1 action","volume":"115","author":"Nagaraj","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4437","DOI":"10.18632\/oncotarget.27055","article-title":"Identification of ZYG11A as a candidate IGF1-dependent proto-oncogene in endometrial cancer","volume":"10","author":"Achlaug","year":"2019","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ejca.2020.09.034","article-title":"Identification of nephronectin as a new target for IGF1 action","volume":"141","author":"Sarfstein","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Shibel, R., Sarfstein, R., Nagaraj, K., Lapkina-Gendler, L., Laron, Z., Dixit, M., Yakar, S., and Werner, H. (2021). The olfactory receptor gene product, OR5H2, modulates endometrial cancer cells proliferation via interaction with the IGF1 signaling pathway. Cells, 10.","DOI":"10.3390\/cells10061483"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Werner, H., Sarfstein, R., Nagaraj, K., and Laron, Z. (2020). Laron syndrome research paves the way for new insights in oncological investigation. Cells, 9.","DOI":"10.3390\/cells9112446"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/07853890701771823","article-title":"MicroRNAs: A new class of gene regulators","volume":"40","author":"Guarnieri","year":"2008","journal-title":"Ann. Med."},{"key":"ref_45","first-page":"354","article-title":"The impact of microRNAs on endocrinology","volume":"8","author":"Zalts","year":"2011","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1126\/science.1151651","article-title":"Gene regulation by transcription factors and microRNAs","volume":"319","author":"Hobert","year":"2008","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"S20","DOI":"10.1038\/ng1803","article-title":"Canalization of development by microRNAs","volume":"38","author":"Hornstein","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.trsl.2011.01.013","article-title":"MicroRNAs as therapeutic targets in cancer","volume":"157","author":"Croce","year":"2011","journal-title":"Transl. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/BJ20100859","article-title":"MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells","volume":"432","author":"Jiang","year":"2010","journal-title":"Biochem J."},{"key":"ref_50","first-page":"1505","article-title":"MicroRNA-320a acts as a tumor suppressor in endometrial carcinoma by targeting IGF-1R","volume":"43","author":"Shu","year":"2019","journal-title":"Int. J. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4910","DOI":"10.1038\/onc.2011.197","article-title":"A novel oncogenic mechanism in Ewing sarcoma involving IGF pathway targeting by EWS\/Fli1-regulated microRNAs","volume":"30","author":"McKinsey","year":"2011","journal-title":"Oncogene"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Dobre, M., Herlea, V., Vladut, C., Ciocirlan, M., Balaban, V.D., Constantinescu, G., Diculescu, M., and Milanesi, E. (2021). Dysregulation of miRNAs targeting the IGF-1R pathway in pancreatic ductal adenocarcinoma. Cells, 10.","DOI":"10.3390\/cells10081856"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"701246","DOI":"10.3389\/fendo.2021.701246","article-title":"GH and IGF system: The regulatory role of miRNAs and lncRNAs in cancer","volume":"12","author":"Catellani","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1159\/000504669","article-title":"The role of microRNAs in influencing body growth and development","volume":"93","author":"Cirillo","year":"2020","journal-title":"Horm. Res. Paediatr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nm.2186","article-title":"MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis","volume":"16","author":"Anand","year":"2010","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1172\/JCI79052","article-title":"MicroRNA-132 enhances transition from inflammation to proliferation during wound healing","volume":"125","author":"Li","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8465","DOI":"10.1038\/s41598-018-26547-6","article-title":"SIRT1, miR-132 and miR-212 link human longevity to Alzheimer\u2019s Disease","volume":"8","author":"Hadar","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11357-011-9340-3","article-title":"Gene set analysis of GWAS data for human longevity highlights the relevance of the insulin\/IGF-1 signaling and telomere maintenance pathways","volume":"35","author":"Deelen","year":"2013","journal-title":"Age"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10549-020-06037-y","article-title":"N-myristoyltransferase proteins in breast cancer: Prognostic relevance and validation as a new drug target","volume":"186","author":"Mackey","year":"2021","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"111003","DOI":"10.1016\/j.mce.2020.111003","article-title":"Role of the GH-IGF1 system in progression of cancer","volume":"518","author":"Werner","year":"2020","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.tem.2008.03.003","article-title":"IGF signaling defects as causes of growth failure and IUGR","volume":"19","author":"Klammt","year":"2008","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.4158\/EP15939.RA","article-title":"Lessons from 50 years of study of Laron syndrome","volume":"21","author":"Laron","year":"2015","journal-title":"Endocr. Pract."},{"key":"ref_63","first-page":"6","article-title":"Fifty years on: New lessons from Laron syndrome","volume":"19","author":"Werner","year":"2017","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ghir.2014.03.006","article-title":"Transcriptional and epigenetic control of IGF1R gene expression: Implications in metabolism and cancer","volume":"24","author":"Werner","year":"2014","journal-title":"Growth Horm. IGF Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1002\/jcp.24217","article-title":"The decline and fall of the IGF-I receptor","volume":"28","author":"Baserga","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0092-8674(01)00306-3","article-title":"A conserved regulatory system for aging","volume":"105","author":"Kenyon","year":"2001","journal-title":"Cell"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S1096-6374(03)00038-8","article-title":"Serum levels of insulin-like growth factor I and its binding proteins in health and disease","volume":"13","author":"Juul","year":"2003","journal-title":"Growth Horm IGF Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.critrevonc.2013.01.005","article-title":"The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer","volume":"87","author":"Anisimov","year":"2013","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"17737","DOI":"10.1038\/s41598-017-18175-3","article-title":"Urinary miR-21 as a potential biomarker of hypertensive kidney injury and fibrosis","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1080\/01443615.2020.1820465","article-title":"Expression levels of maternal plasma microRNAs in preeclamptic pregnancies","volume":"41","author":"Ayaz","year":"2021","journal-title":"J. Obstet. Gynecol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.bbrc.2020.05.090","article-title":"Brown adipocyte-derived exosomal miR-132-3p suppress hepatic Srebf1 expression and thereby attenuate expression of lipogenic genes","volume":"530","author":"Kariba","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"770","DOI":"10.3389\/fphar.2017.00770","article-title":"Advances in roles of miR-132 in the nervous system","volume":"8","author":"Qian","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"30953","DOI":"10.1038\/srep30953","article-title":"microRNA-132\/212 deficiency enhances A\u03b2 production and senile plaque deposition in Alzheimer\u2019s disease triple transgenic mice","volume":"6","author":"Rainone","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"87","DOI":"10.14348\/molcells.2016.2318","article-title":"Sirt1 and the mitochondria","volume":"39","author":"Tang","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Leite, J.A., Ghirotto, B., Targhetta, V.P., de Lima, J., and C\u00e2mara, N.O.S. (2021). Sirtuins as pharmacological targets in neurodegenerative and neuropsychiatric disorders. Br. J. Pharmacol., Online ahead of print.","DOI":"10.1111\/bph.15570"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1210\/me.2009-0117","article-title":"MicroRNA 132 regulates nutritional stress-induced chemokine production through repression of SirT1","volume":"23","author":"Strum","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3233\/JAD-210132","article-title":"The protective mechanism of SIRT1 in the regulation of mitochondrial biogenesis and mitochondrial autophagy in Alzheimer\u2019s Disease","volume":"82","author":"Ye","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.2174\/1570159X18666200729111744","article-title":"SIRT1 promotes neuronal fortification in neurodegenerative diseases through attenuation of pathological hallmarks and enhancement of cellular lifespan","volume":"19","author":"Mishra","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/acel.12219","article-title":"Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence","volume":"13","author":"Tran","year":"2014","journal-title":"Aging Cell"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1210\/jc.2011-1377","article-title":"Meta-analysis and dose-response metaregression: Circulating insulin-like growth factor I (IGF-I) and mortality","volume":"96","author":"Burgers","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1210\/jc.2008-2138","article-title":"Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations","volume":"94","author":"Friedrich","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1016\/j.cmet.2016.05.014","article-title":"The somatotropic axis in human aging: Framework for the current state of knowledge and future research","volume":"23","author":"Milman","year":"2016","journal-title":"Cell Metab."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Zhang, W.B., Ye, K., Barzilai, N., and Milman, S. (2021). The antagonistic pleiotropy of insulin-like growth factor 1. Aging Cell, 313443.","DOI":"10.1111\/acel.13443"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1210\/er.2018-00216","article-title":"Growth hormone deficiency: Health and longevity","volume":"40","author":"Bartke","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.tem.2011.07.004","article-title":"Pleiotropic effects of growth hormone signaling in aging","volume":"22","author":"Bartke","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1152\/physrev.00006.2012","article-title":"Somatotropic signaling: Trade-offs between growth, reproductive development, and longevity","volume":"93","author":"Bartke","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1073\/pnas.0405775102","article-title":"Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands","volume":"102","author":"Broughton","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1198\/016214504000000683","article-title":"A model-based background adjustment for oligonucleotide expression arrays","volume":"99","author":"Wu","year":"2004","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1093\/bioinformatics\/19.2.185","article-title":"A comparison of normalization methods for high density oligonucleotide array data based on variance and bias","volume":"19","author":"Bolstad","year":"2003","journal-title":"Bioinformatics"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","article-title":"Exploration, normalization, and summaries of high density oligonucleotide array probe level data","volume":"4","author":"Irizarry","year":"2003","journal-title":"Biostatistics"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1093\/nar\/gng015","article-title":"Summaries of Affymetrix GeneChip probe level data","volume":"31","author":"Irizarry","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11861\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:24:21Z","timestamp":1760167461000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/21\/11861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,1]]},"references-count":93,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222111861"],"URL":"https:\/\/doi.org\/10.3390\/ijms222111861","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,1]]}}}