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How can we overcome the problem of resistance of the senescent cells to senolytics?

Image credit: http://www.longlonglife.org/en/transhumanism-longevity/anti-aging-supplements/senolytics-the-war-on-senescence-is-on/

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AK
Apoorva Kulkarni Sep 25, 2020

[1]Kang C. Senolytics and Senostatics: A Two-Pronged Approach to Target Cellular Senescence for Delaying Aging and Age-Related Diseases. Mol Cells [Internet]. 2019 Dec 31;42(12):821–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/31838837

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Creative contributions

Targeting SCAPS

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Jamila
Jamila Sep 28, 2020

[1]Kirkland, James L., and Tamar Tchkonia. "Senolytic drugs: from discovery to translation." Journal of internal medicine (2020).

[2]Yosef, Reut, et al. "Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL." Nature communications 7.1 (2016): 1-11.

[3]Nakajima, Wataru, et al. "Combination with vorinostat overcomes ABT-263 (navitoclax) resistance of small cell lung cancer." Cancer biology & therapy 17.1 (2016): 27-35.

CAR T cells as Senolytics

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Antonio Carusillo
Antonio Carusillo Oct 05, 2020

[1]Grezella C, Fernandez-Rebollo E, Franzen J, Ventura Ferreira MS, Beier F, Wagner W. Effects of senolytic drugs on human mesenchymal stromal cells. Stem Cell Res Ther. 2018;9(1):108. Published 2018 Apr 18. doi:10.1186/s13287-018-0857-6

[2]Cardiac Glycosides as Senolytic Compounds, Martin, Nadine et al.Trends in Molecular Medicine, Volume 26, Issue 3, 243 – 245

[3]Halim L, Maher J. CAR T-cell immunotherapy of B-cell malignancy: the story so far. Therapeutic Advances in Vaccines and Immunotherapy. January 2020. doi:10.1177/2515135520927164

[4]Amor, C., Feucht, J., Leibold, J. et al. Senolytic CAR T cells reverse senescence-associated pathologies. Nature 583, 127–132 (2020). https://doi.org/10.1038/s41586-020-2403-9

Targeting BCL-XL with CRISPR

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Jamila
Jamila Oct 06, 2020

[1]Yosef, Reut, et al. "Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL." Nature communications 7.1 (2016): 1-11.

[2]Zhu, Yi, et al. "New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463." Aging (Albany NY) 9.3 (2017): 955.

Combinatorial drug treatment

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Shubhankar Kulkarni
Shubhankar Kulkarni Sep 25, 2020

DNA damage-induced senescence promotes senolytic sensitivity

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Shubhankar Kulkarni
Shubhankar Kulkarni Sep 25, 2020

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