細胞老化研究部｜部門紹介

最終更新日 : 2023年8月8日

部の紹介　

私たちの体を構成する細胞は加齢と伴に「細胞老化」をおこします。細胞老化はあらゆるストレスによって誘導され、がんをはじめとするさまざまな加齢性疾患の発症や個体老化において重要な役割を担っていると考えられています。私たちは細胞老化の分子機構を解析し、がんと老化を制御することを目指しています。

より詳細な研究内容は、オリジナルホームページをご覧ください。

研究内容

細胞老化はさまざまな発がんの危険性のあるストレスによって誘導され、がん抑制機構として働く一方で、加齢と伴に体内に蓄積した老化細胞がさまざまな炎症性蛋白質を高発現し周囲に分泌するSASP (Senescence-associated secretory phenotype)をおこすことが知られています。そして、老化細胞が分泌するSASP因子によって、がんをはじめとする加齢性疾患が引き起こされることが明らかとなってきました。私たちは細胞老化でSASPがおこる分子メカニズムの解析を行うことで、細胞老化の発がんへの関与を明らかにしようと試みています。さらに、個体の老化現象の基礎機構として働く細胞老化を研究することで、「老化」という生命現象の解明を目指しています。

より詳細な研究内容は、オリジナルホームページをご覧ください。

代表論文

Miyata, K., Zhou, X., Nishio, M., Hanyu, A., Chiba, M., Kawasaki, H., Osako, T., Takeuchi, K., Ohno, S., Ueno, T., Maruyama, R. and Takahashi, A.: Chromatin conformational changes at human satellite II contribute to the senescence phenotype in the tumor microenvironment.
Proc. Natl. Acad. Sci. U. S. A., 120, e2305046120 (2023)
Misawa, T., Hitomi, K., Miyata, K., Tanaka, Y., Fujii, R., Chiba, M., Loo, T.M., Hanyu, A., Kawasaki, H., Kato, H., Maezawa, Y., Yokote, K., Nakamura, A.J., Ueda, K., Yaegashi, N. & _*Takahashi, A.: Identification of novel senescent markers in small extracellular vesicles.
International Journal of Molecular Sciences, 24 (3), 2421, 2023
Ebata, H., Loo, T.M. and Takahashi, A.: Telomere Maintenance and the cGAS-STING Pathway in Cancer.
Cells, 11(12), 1958, 2022
Sugawara, S., Okada, R., Loo, T.M., Tanaka, H., Miyata, K., Chiba, M., Kawasaki, H., Katoh, K., Kaji, S., Maezawa, Y., Yokote, K., Nakayama, M., Oshima, M., Nagao, K., Obuse, C., Nagayama, S., Nakanishi, A., Kanemaki, MT., Hara, E. and Takahashi, A.: RNaseH2A downregulation drives chromosomal DNA fragmentation and accumulation of RNA-DNA hybrids in senescent cells.
Communications Biology, 5, 1420(2022).
Igarashi, N., Miyata, K., Loo, T.M., Chiba, M., Hanyu, A., Nishio, M., Kawasaki, H., Zheng, H., Toyokuni, S., Kon, S., Moriyama, K., Fujita, Y. and Takahashi, A.: Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells.
Nature Communications, 13, 4157, (2022).
Okumura, S., Konishi, Y., Narukawa, M., Sugiura, Y, Yoshimoto, S., Arai, Y., Sato, S., Yoshida, Y., Tsuji, S., Uemura, K., Wakita, M., Matsudaira, T., Matsumoto, T., Kawamoto, S., Takahashi, A., Itatani, Y., Miki, H., Takamatsu, M, Obama, K., Takeuchi, K., Suematsu, M., Ohtani, N., Fukunaga, Y., Ueno, M., Sakai, Y., Nagayama, S. and Hara, E.: Identification of gut bacteria abundant in CRC patients that promote tumourigenesis via butyrate secretion.
Nature Communications, 12(1), 5674 (2021)
Miyata, K., Imai, Y., Hori, S., Nishio, M., Loo, T.M., Okada, R., Yang, L., Nakadai, T., Maruyama, R., Fujii, R., Ueda, K., Jiang, Li., Zheng, H., Toyokuni, S., Sakata, T., Shirahige, K., Kojima, R., Nakayama, M., Oshima, M., Nagayama, S., Seimiya, H., Hirota, T., Saya, H., Hara, E. and Takahashi, A.: Pericentromeric noncoding RNA changes DNA binding of CTCF and inflammatory gene expression in senescence and cancer.
Proc. Natl. Acad. Sci. U.S.A., 118(35), e2025647118 (2021)
Obara, R., Kamiya, M., Tanaka, Y., Kojima, R., Kawaguchi, T., Sugawara, M., Takahashi, A., Noda, T. and Urano, Y.: GGT-activatable fluorescence probe for durable tumor imaging.
Angewandte Chemie Int. Edi., 60(4), 2125-2129 (2021)
Hitomi, K., Okada, R., Loo, T.M., Miyata, K., Nakamura, A.J. and Takahashi, A.: DNA damage regulates senescence-associated extracellular vesicle release via the ceramide pathway to prevent excessive inflammatory responses.
International Journal of Molecular Sciences, 21(10), 3720 (2020)
Wakita, M., Takahashi, A., Sano, O., Loo, T.M., Imai, Y., Narukawa, M., Iwata, H., Matsudaira, T., Kawamoto, K., Ohtani, N., Yoshimori, T. and Hara, E.: A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells.
Nature Communications, 11, 1935 doi: 10.1038/s41467-020-15719-6 (2020).
Loo, T.M., Miyata, K., Tanaka, Y., & Takahashi, A.: Cancer Science, 111, 304-311 (2020)
Takahashi, A., Loo, T.M., Okada, R., Kamachi, F., Watanabe, Y., Wakita, M., Watanabe, S., Kawamoto, S., Miyata, K., Barber, G.N., Ohtani, N. and Hara, E.: Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells.
Nature Communications, 9, 1249 doi:10.1038/s41467-018-03555-8 (2018).
Takasugi, M., Okada, R., Takahashi, A., Chen, D., Watanabe, S., Hara, E.: Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2.
Nature Communications, 8, 15729 doi:10.1038/ncomms15728 (2017).
*Takahashi, A., Okada, R., Nagao, K., Kawamata, Y., Hanyu, A., Yoshimoto, S., Takasugi, M., Watanabe, S., Kanemaki, M., Obuse, C. and *Hara, E.: Exosomes maintain cellular homeostasis by excreting harmful DNA from cells.
Nature Communications, 8, 15287 (2017)
(*Takahashi and Hara are co-corresponding to this paper.)
*Sato, S., *Kawamata, Y., *Takahashi, A., *Imai, Y., Hanyu, A., Okuma, A., Takasugi, M., Yamakoshi, K, Sorimachi, H., Sone, S., Nishioka, Y, Ohtani, N. and Hara, E.: Ablation of the p16INK4a tumour suppressor reverses ageing phenotypes of klotho mice.
Nature Communications, 6: 7035 doi: 10.1038/ncomms8035 (2015).
(*Sato, Kawamata, Takahashi and Imai contributed equally to this paper.)
Imai, Y., Takahashi, A., Hanyu, A., Hori, S., Sato, S., Naka, K., Hirao, A., Ohtani, N. and Hara, E.: Crosstalk between the Rb Pathway and AKT Signaling Forms a Quiescence-Senescence Switch.
Cell Rep., 7, 194-207 (2014)　
Takahashi, A., Imai, Y., Yamakoshi, K., Kuninaka, S., Ohtani, N., Yoshimoto, S., Hori, S., Tachibana, M., Anderton, E., Takeuchi, T., Shinkai, Y., Peters, G., Saya, H. & Hara, E..: DNA Damage Signaling Triggers Degradation of Histone Methyltransferases through APC/C(Cdh1) in Senescent Cells.
Mol Cell. 45, 123-131 (2012)
Takeuchi, S., Takahashi, A., Motoi, N., Tajima, T., Yamakoshi, K., Yoshimoto, S., Hirao, A., Yanagi, S., Fukami, K., Ishikawa, Y., Sone, S. & Hara, E..: Intrinsic cooperation between p16INK4a and p21Waf1/Cip1 in the onset of cellular senescence and tumor suppression in vivo.
Cancer Res. 70, 9381-9390 (2010)
*Yamakoshi, K., *Takahashi, A., Hirose, F., Nakayama, R., Ishimaru, N., Kubo, Y., Mann, D.J., Ohmura, M., Hirao, A., Saya, H., Arase, S., Hayashi, Y., Nakao, K., Matsumoto, M., Ohtani, N. & Hara, E..: Real-time in vivo imaging of p16Ink4a reveals crosstalk with p53
J. Cell Biol., 186, 393-407 (2009)
(*Yamakoshi and Takahashi contributed equally to this paper.)
Takahashi, A., Ohtani, N., Yamakoshi, K., Iida, S., Tahara, H.,Nakayama, K., Nakayama, K.I., Ide, T., Saya, H. & Hara, E..: Mitogenic signalling and the p16INK4a/Rb pathway co-operate to enforce irreversible cellular senescence
Nature Cell Biol., 8, 1291-1297 (2006)

連絡先

高橋暁子(部長)
〒135-8550　江東区有明3-8-31
Tel：03-3570-0605　Fax：03-3570-0457
E-mail：akiko.takahashi@jfcr.or.jp