Aging of spermatogonial stem cells by Jnk-mediated glycolysis activation

Mito Kanatsu-Shinohara, Takuya Yamamoto, Hidehiro Toh, Yasuhiro Kazuki, Kanako Kazuki, Junichi Imoto, Kazuho Ikeo, Motohiko Oshima, Katsuhiko Shirahige, Atsushi Iwama, Yoichi Nabeshima, Hiroyuki Sasaki, Takashi Shinohara

研究成果: ジャーナルへの寄稿記事

抄録

Because spermatogonial stem cells (SSCs) are immortal by serial transplantation, SSC aging in intact testes is considered to be caused by a deteriorated microenvironment. Here, we report a cell-intrinsic mode of SSC aging by glycolysis activation. Using cultured SSCs, we found that aged SSCs proliferated more actively than young SSCs and showed enhanced glycolytic activity. Moreover, they remained euploid and exhibited stable androgenetic imprinting patterns with robust SSC activity despite having shortened telomeres. Aged SSCs showed increased Wnt7b expression, which was associated with decreased Polycomb complex 2 activity. Our results suggest that aberrant Wnt7b expression activated c-jun N-terminal kinase (JNK), which down-regulated mitochondria numbers by suppressing Ppargc1a. Down-regulation of Ppargc1a probably decreased reactive oxygen species and enhanced glycolysis. Analyses of the Klotho-deficient aging mouse model and 2-y-old aged rats confirmed JNK hyperactivation and increased glycolysis. Therefore, not only microenvironment but also intrinsic activation of JNK-mediated glycolysis contributes to SSC aging.

元の言語英語
ページ(範囲)16404-16409
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
116
発行部数33
DOI
出版物ステータス出版済み - 8 13 2019

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Glycolysis
Stem Cells
JNK Mitogen-Activated Protein Kinases
Cell Aging
Telomere Shortening
Testis
Reactive Oxygen Species
Mitochondria
Down-Regulation
Transplantation

All Science Journal Classification (ASJC) codes

  • General

これを引用

Kanatsu-Shinohara, M., Yamamoto, T., Toh, H., Kazuki, Y., Kazuki, K., Imoto, J., ... Shinohara, T. (2019). Aging of spermatogonial stem cells by Jnk-mediated glycolysis activation. Proceedings of the National Academy of Sciences of the United States of America, 116(33), 16404-16409. https://doi.org/10.1073/pnas.1904980116

Aging of spermatogonial stem cells by Jnk-mediated glycolysis activation. / Kanatsu-Shinohara, Mito; Yamamoto, Takuya; Toh, Hidehiro; Kazuki, Yasuhiro; Kazuki, Kanako; Imoto, Junichi; Ikeo, Kazuho; Oshima, Motohiko; Shirahige, Katsuhiko; Iwama, Atsushi; Nabeshima, Yoichi; Sasaki, Hiroyuki; Shinohara, Takashi.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 116, 番号 33, 13.08.2019, p. 16404-16409.

研究成果: ジャーナルへの寄稿記事

Kanatsu-Shinohara, M, Yamamoto, T, Toh, H, Kazuki, Y, Kazuki, K, Imoto, J, Ikeo, K, Oshima, M, Shirahige, K, Iwama, A, Nabeshima, Y, Sasaki, H & Shinohara, T 2019, 'Aging of spermatogonial stem cells by Jnk-mediated glycolysis activation', Proceedings of the National Academy of Sciences of the United States of America, 巻. 116, 番号 33, pp. 16404-16409. https://doi.org/10.1073/pnas.1904980116
Kanatsu-Shinohara, Mito ; Yamamoto, Takuya ; Toh, Hidehiro ; Kazuki, Yasuhiro ; Kazuki, Kanako ; Imoto, Junichi ; Ikeo, Kazuho ; Oshima, Motohiko ; Shirahige, Katsuhiko ; Iwama, Atsushi ; Nabeshima, Yoichi ; Sasaki, Hiroyuki ; Shinohara, Takashi. / Aging of spermatogonial stem cells by Jnk-mediated glycolysis activation. :: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; 巻 116, 番号 33. pp. 16404-16409.
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abstract = "Because spermatogonial stem cells (SSCs) are immortal by serial transplantation, SSC aging in intact testes is considered to be caused by a deteriorated microenvironment. Here, we report a cell-intrinsic mode of SSC aging by glycolysis activation. Using cultured SSCs, we found that aged SSCs proliferated more actively than young SSCs and showed enhanced glycolytic activity. Moreover, they remained euploid and exhibited stable androgenetic imprinting patterns with robust SSC activity despite having shortened telomeres. Aged SSCs showed increased Wnt7b expression, which was associated with decreased Polycomb complex 2 activity. Our results suggest that aberrant Wnt7b expression activated c-jun N-terminal kinase (JNK), which down-regulated mitochondria numbers by suppressing Ppargc1a. Down-regulation of Ppargc1a probably decreased reactive oxygen species and enhanced glycolysis. Analyses of the Klotho-deficient aging mouse model and 2-y-old aged rats confirmed JNK hyperactivation and increased glycolysis. Therefore, not only microenvironment but also intrinsic activation of JNK-mediated glycolysis contributes to SSC aging.",
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AU - Kazuki, Kanako

AU - Imoto, Junichi

AU - Ikeo, Kazuho

AU - Oshima, Motohiko

AU - Shirahige, Katsuhiko

AU - Iwama, Atsushi

AU - Nabeshima, Yoichi

AU - Sasaki, Hiroyuki

AU - Shinohara, Takashi

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