The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells
Aging is known to be the single most important risk factor for multiple diseases. Sirtuin 6, or SIRT6, has recently been identified as a critical regulator of transcription, genome stability, telomere integrity, DNA repair, and metabolic homeostasis. A knockout mouse model of SIRT6 has displayed dra...
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| Published in: | The Journal of biological chemistry Vol. 288; no. 25; p. 18439 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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United States
21.06.2013
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| ISSN: | 1083-351X, 1083-351X |
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| Abstract | Aging is known to be the single most important risk factor for multiple diseases. Sirtuin 6, or SIRT6, has recently been identified as a critical regulator of transcription, genome stability, telomere integrity, DNA repair, and metabolic homeostasis. A knockout mouse model of SIRT6 has displayed dramatic phenotypes of accelerated aging. In keeping with its role in aging, we demonstrated that human dermal fibroblasts (HDFs) from older human subjects were more resistant to reprogramming by classic Yamanaka factors than those from younger human subjects, but the addition of SIRT6 during reprogramming improved such efficiency in older HDFs substantially. Despite the importance of SIRT6, little is known about the molecular mechanism of its regulation. We show, for the first, time posttranscriptional regulation of SIRT6 by miR-766 and inverse correlation in the expression of this microRNA in HDFs from different age groups. Our results suggest that SIRT6 regulates miR-766 transcription via a feedback regulatory loop, which has implications for the modulation of SIRT6 expression in reprogramming of aging cells. |
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| AbstractList | Aging is known to be the single most important risk factor for multiple diseases. Sirtuin 6, or SIRT6, has recently been identified as a critical regulator of transcription, genome stability, telomere integrity, DNA repair, and metabolic homeostasis. A knockout mouse model of SIRT6 has displayed dramatic phenotypes of accelerated aging. In keeping with its role in aging, we demonstrated that human dermal fibroblasts (HDFs) from older human subjects were more resistant to reprogramming by classic Yamanaka factors than those from younger human subjects, but the addition of SIRT6 during reprogramming improved such efficiency in older HDFs substantially. Despite the importance of SIRT6, little is known about the molecular mechanism of its regulation. We show, for the first, time posttranscriptional regulation of SIRT6 by miR-766 and inverse correlation in the expression of this microRNA in HDFs from different age groups. Our results suggest that SIRT6 regulates miR-766 transcription via a feedback regulatory loop, which has implications for the modulation of SIRT6 expression in reprogramming of aging cells. Aging is known to be the single most important risk factor for multiple diseases. Sirtuin 6, or SIRT6, has recently been identified as a critical regulator of transcription, genome stability, telomere integrity, DNA repair, and metabolic homeostasis. A knockout mouse model of SIRT6 has displayed dramatic phenotypes of accelerated aging. In keeping with its role in aging, we demonstrated that human dermal fibroblasts (HDFs) from older human subjects were more resistant to reprogramming by classic Yamanaka factors than those from younger human subjects, but the addition of SIRT6 during reprogramming improved such efficiency in older HDFs substantially. Despite the importance of SIRT6, little is known about the molecular mechanism of its regulation. We show, for the first, time posttranscriptional regulation of SIRT6 by miR-766 and inverse correlation in the expression of this microRNA in HDFs from different age groups. Our results suggest that SIRT6 regulates miR-766 transcription via a feedback regulatory loop, which has implications for the modulation of SIRT6 expression in reprogramming of aging cells.Aging is known to be the single most important risk factor for multiple diseases. Sirtuin 6, or SIRT6, has recently been identified as a critical regulator of transcription, genome stability, telomere integrity, DNA repair, and metabolic homeostasis. A knockout mouse model of SIRT6 has displayed dramatic phenotypes of accelerated aging. In keeping with its role in aging, we demonstrated that human dermal fibroblasts (HDFs) from older human subjects were more resistant to reprogramming by classic Yamanaka factors than those from younger human subjects, but the addition of SIRT6 during reprogramming improved such efficiency in older HDFs substantially. Despite the importance of SIRT6, little is known about the molecular mechanism of its regulation. We show, for the first, time posttranscriptional regulation of SIRT6 by miR-766 and inverse correlation in the expression of this microRNA in HDFs from different age groups. Our results suggest that SIRT6 regulates miR-766 transcription via a feedback regulatory loop, which has implications for the modulation of SIRT6 expression in reprogramming of aging cells. |
| Author | Sharma, Amit Diecke, Sebastian He, Chunjiang Wu, Joseph C Zhang, Wendy Y Lan, Feng Mordwinkin, Nicholas M Chua, Katrin F |
| Author_xml | – sequence: 1 givenname: Amit surname: Sharma fullname: Sharma, Amit organization: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA – sequence: 2 givenname: Sebastian surname: Diecke fullname: Diecke, Sebastian – sequence: 3 givenname: Wendy Y surname: Zhang fullname: Zhang, Wendy Y – sequence: 4 givenname: Feng surname: Lan fullname: Lan, Feng – sequence: 5 givenname: Chunjiang surname: He fullname: He, Chunjiang – sequence: 6 givenname: Nicholas M surname: Mordwinkin fullname: Mordwinkin, Nicholas M – sequence: 7 givenname: Katrin F surname: Chua fullname: Chua, Katrin F – sequence: 8 givenname: Joseph C surname: Wu fullname: Wu, Joseph C |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23653361$$D View this record in MEDLINE/PubMed |
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| Keywords | Gene Expression MicroRNA Induced pluripotent Stem Cells Molecular Biology Aging Transcription Factors Embryonic Stem Cell |
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| Snippet | Aging is known to be the single most important risk factor for multiple diseases. Sirtuin 6, or SIRT6, has recently been identified as a critical regulator of... |
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| SubjectTerms | Adolescent Age Factors Aging - genetics Aging - physiology Cells, Cultured Cellular Reprogramming - genetics Cellular Reprogramming - physiology Cluster Analysis Dermis - cytology Embryoid Bodies - metabolism Embryoid Bodies - physiology Fibroblasts - cytology Fibroblasts - metabolism Fibroblasts - physiology Gene Expression Profiling Humans Immunohistochemistry Induced Pluripotent Stem Cells - metabolism Induced Pluripotent Stem Cells - physiology MicroRNAs - genetics Middle Aged Models, Genetic Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - physiology Reverse Transcriptase Polymerase Chain Reaction RNA Processing, Post-Transcriptional Sirtuins - genetics Sirtuins - metabolism Sirtuins - physiology |
| Title | The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells |
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