Catalyst Awardee

Project Description

Compounds that suppress the aging process through selective autophagy

Arimoto Hirokazu, PhD

Competition Sponsor: Japan Agency for Medical Research and Development

Autophagy is a major degradation system in cells. Best known is its ability to degrade existing proteins into amino acids during starvation. Autophagy also plays a vital role in the protection of the human body by removing invading pathogens and harmful substances such as protein aggregates that accumulate along the aging process. If we can target and remove harmful substances from cells, we would be able to expect to slow down the aging process and reduce the chance of diseases.

Toward this goal, we recently developed a new method named AUTAC (Autophagy-targeting chimera) in 2019. This method uses a combination of a “”targeting ligand”” to select a degradation target and a “”degradation tag””, a very unique compound that can trigger autophagy. By changing the targeting ligand appropriately, autophagic degradation of various intracellular substances can be boosted. We believe this is the first example of an autophagy-promoting compound with the ability to “”select a degradation target.

In this NAM-HLGC research and development, we will create a variety of AUTAC compounds to realize a long and healthy life. Specifically, we aim to eliminate protein aggregates and dysfunctional mitochondria that accumulate in cells. Since dysfunctional mitochondria are involved in the production of inflammatory cytokines and reactive oxygen species, their removal is expected to inhibit chronic tissue inflammation, neurodegenerative diseases, and cancer. Chronic inflammation is itself a hallmark of aging, and is thought to be a cause of age-related diseases such as cancer and metabolic disorders. In addition, we will analyze the mechanism of AUTAC function to further improve its function.

Sign up for updates