Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence
Abstract The “Mlx” and “Myc” transcription factor networks cross‐communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max‐like factor Mlx associate with the Myc‐like factors MondoA or ChREBP. The c...
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| Format: | Article |
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Wiley
2024-09-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202401593 |
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| author | Huabo Wang Taylor Stevens Jie Lu Alexander Roberts Clinton Van't Land Radhika Muzumdar Zhenwei Gong Jerry Vockley Edward V. Prochownik |
| author_facet | Huabo Wang Taylor Stevens Jie Lu Alexander Roberts Clinton Van't Land Radhika Muzumdar Zhenwei Gong Jerry Vockley Edward V. Prochownik |
| author_sort | Huabo Wang |
| collection | DOAJ |
| description | Abstract The “Mlx” and “Myc” transcription factor networks cross‐communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max‐like factor Mlx associate with the Myc‐like factors MondoA or ChREBP. The current work demonstrates that body‐wide Mlx inactivation, like that of Myc, accelerates numerous aging‐related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging‐related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability, and aging. Whereas “MycKO” mice have an extended lifespan because of a lower cancer incidence, “MlxKO” mice have normal lifespans and a higher cancer incidence. Like Myc, the expression of Mlx, MondoA, and ChREBP and their control over their target genes deteriorate with age in both mice and humans. Collectively, these findings underscore the importance of lifelong and balanced cross‐talk between the two networks to maintain proper function and regulation of the many factors that can affect normal aging. |
| format | Article |
| id | doaj-art-21d46c4a8a1c4ee19059c58c19da19c0 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-21d46c4a8a1c4ee19059c58c19da19c02025-08-20T01:55:19ZengWileyAdvanced Science2198-38442024-09-011134n/an/a10.1002/advs.202401593Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer IncidenceHuabo Wang0Taylor Stevens1Jie Lu2Alexander Roberts3Clinton Van't Land4Radhika Muzumdar5Zhenwei Gong6Jerry Vockley7Edward V. Prochownik8Division of Hematology/Oncology UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Hematology/Oncology UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Hematology/Oncology UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Hematology/Oncology UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Medical Genetics UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Endocrinology UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Endocrinology UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Medical Genetics UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USADivision of Hematology/Oncology UPMC Children's Hospital of Pittsburgh Pittsburgh PA 15201 USAAbstract The “Mlx” and “Myc” transcription factor networks cross‐communicate and share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that the Max‐like factor Mlx associate with the Myc‐like factors MondoA or ChREBP. The current work demonstrates that body‐wide Mlx inactivation, like that of Myc, accelerates numerous aging‐related phenotypes pertaining to body habitus and metabolism. The deregulation of numerous aging‐related Myc target gene sets is also accelerated. Among other functions, these gene sets often regulate ribosomal and mitochondrial structure and function, genomic stability, and aging. Whereas “MycKO” mice have an extended lifespan because of a lower cancer incidence, “MlxKO” mice have normal lifespans and a higher cancer incidence. Like Myc, the expression of Mlx, MondoA, and ChREBP and their control over their target genes deteriorate with age in both mice and humans. Collectively, these findings underscore the importance of lifelong and balanced cross‐talk between the two networks to maintain proper function and regulation of the many factors that can affect normal aging.https://doi.org/10.1002/advs.202401593glycolysismitochondriareactive oxygen speciesTCA cycletelomeresWarburg effect |
| spellingShingle | Huabo Wang Taylor Stevens Jie Lu Alexander Roberts Clinton Van't Land Radhika Muzumdar Zhenwei Gong Jerry Vockley Edward V. Prochownik Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence Advanced Science glycolysis mitochondria reactive oxygen species TCA cycle telomeres Warburg effect |
| title | Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence |
| title_full | Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence |
| title_fullStr | Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence |
| title_full_unstemmed | Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence |
| title_short | Body‐Wide Inactivation of the Myc‐Like Mlx Transcription Factor Network Accelerates Aging and Increases the Lifetime Cancer Incidence |
| title_sort | body wide inactivation of the myc like mlx transcription factor network accelerates aging and increases the lifetime cancer incidence |
| topic | glycolysis mitochondria reactive oxygen species TCA cycle telomeres Warburg effect |
| url | https://doi.org/10.1002/advs.202401593 |
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