Dept. Aging Systems Science

Definition of the fundamental nature of aging through omics-data-driven research and its validation through interventions that suppress aging.

We aim to advance omics-data-driven research to uncover previously unrecognized fundamental aspects of aging, based on the comprehensive evaluation of age-associated changes in gene expression. As a unique approach, we integrate within-species age-associated gene expression changes with cross-species lifespan-associated expression patterns to infer and experimentally validate the detrimental and beneficial components of age-associated changes. In parallel, as a central focus of our research, we investigate the aging proteome and age-related dysregulation of post-transcriptional control to identify novel mechanisms underlying aging and lifespan regulation. We have identified the accumulation of APOE and immunoglobulins as key features of the aging proteome and are advancing studies to elucidate their underlying mechanisms and to develop strategies for suppressing aging.

Research Topics

・Distinction between detrimental and adaptive aspects of aging-associated changes based on cross-species comparative approaches.
・Mechanistic and functional analysis of age-related dysregulation of post-transcriptional control, with a focus on proteome-level alterations.
・Mechanistic and functional analysis of age-associated accumulation of APOE and immunoglobulins as key features of the aging proteome.
・Identification of novel mechanisms of aging and lifespan regulation through large-scale omics data analyses.
・Evaluation and development of interventions to extend healthspan and maximum lifespan in mammalian models.

Selected Publications

1. Takasugi, M., Nonaka, Y. , Takemura, K., Yoshida, Y., Stein, F., Schwarz, J.J., Adachi, J., Satoh, J., Ito, S., Tombline, G., Biashad, S.A., Seluanov, A., Gorbunova, V., Ohtani, N. (2024) An atlas of the aging mouse proteome reveals the features of age-related post-transcriptional dysregulation. Nat Commun 15(1):8520
2. Takasugi, M., Ohtani, N., Takemura, K., Emmrich, S., Zakusilo, F.T., Yoshida, Y., Kutsukake, N., Mariani, J.M., Windrem, M.S., Chandler-Militello, D., Goldman, S.A., Satoh, J., Ito, S., Seluanov, A., Gorbunova, V. (2023) CD44 correlates with longevity and enhances basal ATF6 activity and ER stress resistance. Cell Rep 42(9):113130.
3. Takasugi, M., Yoshida, Y., Nonaka, Y., Ohtani, N. (2023) Gene expressions associated with longer lifespan and aging exhibit similarity in mammals. Nucleic Acids Res. 51(14):7205-7219.
4. Takasugi, M., Firsanov, D., Tombline, G., Ning, H., Ablaeva, J., Seluanov, A., Gorbunova, V. (2020). Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties. Nat Commun 11(1):2376
5. Takasugi, M., Okada, R., Takahashi, A., Virya, C.D., Watanabe, S., Hara, E. (2017). Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2. Nat Commun 8;15729

Research Interests

Aging, multi-omics analysis, and lifespan regulation