HeSReC Healthspan Research Center

Aging, MultiOmics

Molecular mechanisms of aging with a focus on post-transcriptional regulation, proteome dynamics, and multi-omics integration, combined with cross-species comparative approaches to identify conserved and divergent aging processes and targets for healthspan extension.

Aging, Transcriptomics, Proteomics

• Japanese Society of Anti-Aging Medicine
• The Japanese Society for Cell Biology

Our research aims to advance a comprehensive understanding of aging by re-evaluating age-associated gene expression changes beyond the conventional transcriptome-centered framework. To this end, we employ two complementary strategies: proteome-centered multi-omics analyses and cross-species comparative approaches. First, we utilize proteome-centered multi-omics to capture age-related regulatory changes that are not reflected at the transcript level, thereby providing a more functional and mechanistic view of aging biology. Second, we integrate age-associated transcriptomic changes with cross-species transcriptome comparisons to identify conserved and divergent patterns of aging, offering insights into their biological significance. In particular, our research focuses on: (1) elucidating the roles of major protein degradation systems in age-related post-transcriptional dysregulation; (2) investigating the impact of age-dependent accumulation of proteins such as immunoglobulins in aged tissues; and (3) distinguishing detrimental versus adaptive components of age-associated gene expression changes, with the ultimate goal of translating these findings into therapeutic strategies for healthy aging.

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