Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL

Reut Yosef, Noam Pilpel, Ronit Tokarsky-Amiel, Anat Biran, Yossi Ovadya, Snir Cohen, Ezra Vadai, Liat Dassa, Elisheva Shahar, Reba Condiotti, Ittai Ben-Porath*, Valery Krizhanovsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

625 Scopus citations

Abstract

Senescent cells, formed in response to physiological and oncogenic stresses, facilitate protection from tumourigenesis and aid in tissue repair. However, accumulation of such cells in tissues contributes to age-related pathologies. Resistance of senescent cells to apoptotic stimuli may contribute to their accumulation, yet the molecular mechanisms allowing their prolonged viability are poorly characterized. Here we show that senescent cells upregulate the anti-apoptotic proteins BCL-W and BCL-XL. Joint inhibition of BCL-W and BCL-XL by siRNAs or the small-molecule ABT-737 specifically induces apoptosis in senescent cells. Notably, treatment of mice with ABT-737 efficiently eliminates senescent cells induced by DNA damage in the lungs as well as senescent cells formed in the epidermis by activation of p53 through transgenic p14ARF. Elimination of senescent cells from the epidermis leads to an increase in hair-follicle stem cell proliferation. The finding that senescent cells can be eliminated pharmacologically paves the way to new strategies for the treatment of age-related pathologies.

Original languageAmerican English
Article number11190
JournalNature Communications
Volume7
DOIs
StatePublished - 6 Apr 2016

Bibliographical note

Funding Information:
The author was supported in part by the Department of Energy, Office of Science, Office of High Energy Physics, Grant Nos. DE-FG02-08ER41575 and DE-SC0013496.

Fingerprint

Dive into the research topics of 'Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL'. Together they form a unique fingerprint.

Cite this