Catalyst Awardee

Project Description

Clarifying the origins and very early processes of aging in tissue

Susaki Etsuo A., PhD

Competition Sponsor: Japan Agency for Medical Research and Development

Clarifying the origin and progression mechanism of aging inside tissue is the most fundamental and vital question in aging research. However, the rareness of such very early aging foci has prevented the identification and investigation of mechanisms so far due to technical limitations. The genetic property of each species essentially determines the aging process. Mutations of genes involved in genome stability cause premature aging syndromes. Therefore, it is plausibly hypothesized that genome information and its instabilities are the determinants or driving forces of the aging process.

To address these questions, we propose two new research designs: 1) identification and analysis of the very early aging foci inside the tissue, and 2) analysis of genomic instability related to the very early aging process inside tissue by newly developed spatial genomics technique. The first idea will be implemented by the applicant’s CUBIC cell-omics framework (Susaki+ Cell 2014, Susaki+ Nat Commun. 2020, and others). We have already identified potential very early aging foci (sporadic astrocyte foci in the cerebral cortex) by whole-brain CUBIC immunostaining of senescence-related astrocyte marker (GFAP) in young, physiological mouse brains. We are analyzing their inter-tissue structures and functions. We will further investigate the molecular mechanisms by the recent spatial transcriptomics approach. The second idea can be deployed by integrating our developing technologies for whole-cell spatial addressing and single nuclei collection with current genome sequencing analysis. We will analyze the genomes of the cell groups that comprise the very early aging foci by utilizing this spatial genomics technology.
The above ideas are incredibly innovative and unique, as they are based on our globally acclaimed state-of-the-art technology. We will identify essential perturbation points for interventing the aging process from both young and aged individuals. This project will thus provide unique and effective anti-aging strategies, ensuring the realization of a healthy, longevity society.

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