• Title/Summary/Keyword: GDF11

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Parabiosis and Blood Exchange Techniques in Aging Research (개체병렬결합(parabiosis)실험모델과 혈액교환을 이용한 노화(aging)연구 분석)

  • Kyung Tae Chung
    • Journal of Life Science
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    • v.33 no.2
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    • pp.208-215
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    • 2023
  • In recent decades, the field of aging research has progressed from the genetic and cellular levels to in vivo models of blood exchange. Since genes capable of extending the lifespan in C. elegance have been reported, various potential target molecules have been discovered through genomics, proteomics, metabolomics, and transcriptomics. Accordingly, research on the interactions between target molecules has also been increasing. The parabiosis method, in which two experimental animals are surgically combined, was introduced, and a factor that could reverse the aging phenomenon was discovered using this method. The parabiosis method is used to find more accurate and effective aging-reversal factors that could exist in young blood. As more new evidence has been revealed, the parabiosis method has established a new paradigm for aging research. Moreover, a device capable of exchanging blood elaborately in laboratory animals was published in 2022 and presented new results necessary for aging reversal. Since GDF11, was reported, many other anti-aging candidates that are soluble factors in blood, such as β2m, TIMP2, VCAM1, Gpld1, and clusterin, have been discovered. In addition, mcicroglia cells and neuroinflammation have been directly proven to be aging factors. These latest research results were obtained by parabiosis, the newly designed device for plasmapheresis, and injecting young blood or conditioned blood methods. In this review, we discuss the latest research results using the device and young blood administration in old mice.

Gene Expression Profiling in Diethylnitrosamine Treated Mouse Liver: From Pathological Data to Microarray Analysis (Diethylnitrosamine 처리 후 병리학적 결과를 기초로 한 마우스 간에서의 유전자 발현 분석)

  • Kim, Ji-Young;Yoon, Seok-Joo;Park, Han-Jin;Kim, Yong-Bum;Cho, Jae-Woo;Koh, Woo-Suk;Lee, Michael
    • Toxicological Research
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    • v.23 no.1
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    • pp.55-63
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    • 2007
  • Diethylnitrosamine (DEN) is a nitrosamine compound that can induce a variety of liver lesions including hepatic carcinoma, forming DNA-carcinogen adducts. In the present study, microarray analyses were performed with Affymetrix Murine Genome 430A Array in order to identify the gene-expression profiles for DEN and to provide valuable information for the evaluation of potential hepatotoxicity. C57BL/6NCrj mice were orally administered once with DEN at doses of 0, 3, 7 and 20 mg/kg. Liver from each animal was removed 2, 4, 8 and 24 hrs after the administration. The histopathological analysis and serum biochemical analysis showed no significant difference in DEN-treated groups compared to control group. Conversely, the principal component analysis (PCA) profiles demonstrated that a specific normal gene expression profile in control groups differed clearly from the expression profiles of DEN-treated groups. Within groups, a little variance was found between individuals. Student's t-test on the results obtained from triplicate hybridizations was performed to identify those genes with statistically significant changes in the expression. Statistical analysis revealed that 11 genes were significantly downregulated and 28 genes were upregulated in all three animals after 2 h treatment at 20 mg/kg. The upregulated group included genes encoding Gdf15, JunD1, and Mdm2, while the genes including Sox6, Shmt2, and SIc6a6 were largely down regulated. Hierarchical clustering of gene expression also allowed the identification of functionally related clusters that encode proteins related to metabolism, and MAPK signaling pathway. Taken together, this study suggests that match with a toxicant signature can assign a putative mechanism of action to the test compound if is established a database containing response patterns to various toxic compounds.

Identification of Genes Involved in Primordial-primary Follicle Transition by Suppression Subtractive Hybridization

  • Park, Chang-Eun;Yoon, Se-Jin;Jeon, Eun-Hyun;Kim, Young-Hoon;Lee, Sook-Hwan;Lee, Kyung-Ah
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.98-98
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    • 2002
  • Recruitment of primordial follicles(PMF) is crucial for female fertility. however, factors and mechanisms that regulate this process is poorly understood. The present study was conducted to obtain an inclusive view of the gene expression and to identify novel factors and their pathways of regulating PMF arrest and/or growth initiation. Ovaries from one-day neonatal(consists of oocyte and PMF) and five-day old(consists of PMF and primary follicles, PRIF) mice were collected, either total RNA or mRNA was isolated, and suppression subtractive hybridization(SSH) was used to isolate and clone genes that differentially expressed in day 1 and day 5 ovaries. Confirmation that some of these genes are differentially expressed in PMF and/or in PRIF was accomplished by using laser captured microdissection(LCM), RT-PCR. in situ hybridization(ISH) and/or immunohistochemistry(IHC). In toto, 357 clones were sequenced and analyzed by BLAST and RIKEN program. Sequences of 330 clones significantly matched database entries while 27 clones were novel. Forty-two and 47 different genes were identified as differentially expressed in day 1 and day 5 ovaries, respectively, while 7 genes were expressed in both stages of ovaries. Day 5-subtracted library included several genes known as markers far growing follicles, such as ZP2, MATER, and fetuin. Among the genes with assigned functions, 23.8% was associated with cell cycle/apoptosis regulation, 7.1% with cellular structure, 11.9% with metabolism, 26.2% with signal transduction, and 31.0% with gene/protein expression in day 1; while 10.6%, 17.0%, 23.5%, 25.5%, and 23.4% in day 5, respectively. Genes such as GDF-8, Lats2, Septin2, and Weel were the highly expressed genes in PMF, while HSP84, Laminin2, MATER, MTi7, PTP, and Wrn were highly expressed genes in PRIF. We have successfully discovered list of genes expressed in day 1 and day 5 ovaries and confirmed that some of them are differentially expressed in PMF and/or PRIF. Gene expression profile from the present study would provide insight for the future study on the mechanism(s) involved in primordial-primary follicular transition. This work was Supported by Korean Health 21 RND Project, Ministry of Health and Welfare, Korea (01-PJ10-PG6-01GN13-0002).

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