"Dead-cells-derived anti-aging-signal model" and its clinical application

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23738
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0702:Biology at cellular to organismal levels, and related fields
• Research Institution: Tohoku University
• Principal Investigator: Nishizawa Hironari 東北大学, 医学系研究科, 学術研究員 (30846655)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: フェロトーシス / 鉄依存性細胞死 / 脂質過酸化 / 細胞老化

Outline of Final Research Achievements

Ferroptosis is an iron-dependent regulated cell death. However, the effects of secretory signals from ferroptotic cells to surrounding cells were not clear. In this study, we showed that the culture supernatant from ferroptotic cells induced a decrease of SA-β-galactosidase, a senescence-related marker, and cell deaths in neighboring cells. We also found that the propagation of SA-β-galactosidase reduction and cell deaths by the culture supernatant was inhibited by antioxidants and ferroptotic inhibitors. Furthermore, co-culture of ferroptotic cells with normal cells showed that lipid peroxidation and cell deaths propagated to normal cells from ferroptotic cells. These results demonstrate the existence of propagation of lipid peroxidation and ferroptosis by secreted substances from ferroptotic cells.

Free Research Field

細胞死、細胞老化、腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

フェロトーシスは新規に提唱された鉄依存性の細胞死であるが、フェロトーシス細胞からの分泌物質の生体内での機能についてはこれまでほとんど分かっていなかった。本研究によってフェロトーシス細胞から酸化関連物質が分泌されてフェロトーシスが周囲に伝播していくことが明らかになった。この伝播現象が虚血性心疾患などのフェロトーシス関連疾患の病変の拡大に関与していると考えられ、これらの疾患への新治療の開発につながる可能性がある。さらに、フェロトーシスは生体内でがん抑制メカニズムとして働くことが分かっており、フェロトーシスの伝播現象を利用して免疫療法や抗癌剤の効果を増強できる可能性が期待される。