Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell. 2017, 23, 169(1):132-147.e16.

報告日期: 2017/11/21
報告時間: 17:10/18:00
報告學生: 李婉寧
講評老師: 蔣輯武
附件下載: 下載[1670-1506045999-1.pdf] 

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

Peter L.J. de Keizer et al. (2017). Cell 169, 132-147.e116.

Date: November 21st, 2017

Speaker: Wan-Ning Li (李婉寧)

Commentator: Dr. Chi-Wu Chiang (蔣輯武 老師)

Abstract

Cell senescence is a condition that cells are whithdrwan from the cell cycle for a long term of time without undergoing programmed cell death. Persistent senescent cells are thought to be correlated with accelerated aging and the onset of age-related diseases, however, the mechanism of how these damaged cells escape from apoptosis and proceed toward senescence remains largely unclear. In present study, the author identified FOXO4-p53 interaction, which was found invovled in senescence-related pathologies, is critical for determining cell fate. Thus, interfering FOXO4-p53 interaction by FOXO4-DRI, an artificial cell-penetrating peptides (CPPs), was considered to be a potential strategy for disrupting the effect. Furthermore, rather than senolytics such as Quercetin/Desatinib and ABT-263/737, FOXO4-DRI was proved to be more selective and effective to against senescent cells but safe to normal cells. Given the potency of this peptide in vitro, the author then employed the three in vivo senescence-related mice models by monitoring the p16::3MR system to see whether FOXO4-DRI could be applied to therapeutic use. No matter in which of the models, chemotoxicity, accelerated aging, or natural aging, FOXO4-DRI was found powerful to counteract the effect resulted from cell senescence. In conclusion, therapeutically making use of FOXO4-DRI is promising for targeting senescent cells, which may help restoring tissue homeostasis after the loss of health has already occurred.