Treating liver disease by selectively eliminating senescent cells
Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.
1. A method of selectively eliminating senescent cells in a fibrotic liver, the method comprising administering a senolytic agent that consists essentially of a Bcl-xL selective inhibitor, wherein the senolytic agent is administered to the senescent cells in the fibrotic liver intermittently, wherein the intermittent administration is a treatment cycle followed by a non-treatment interval.
2. The method of claim 1 , wherein the senolytic agent is a small molecule inhibitor.
3. The method of claim 1 , wherein the senolytic agent is a polynucleotide or oligonucleotide.
4. The method of claim 3 , wherein the polynucleotide or oligonucleotide is an antisense oligonucleotide, siRNA or shRNA.
5. The method of claim 1 , wherein the non-treatment interval is between at least about 0.5 to 12 months.
6. A method of treating a metabolic syndrome in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an effective amount of a senolytic agent that consists essentially of a Bcl-xL selective inhibitor.
7. The method of claim 6 , wherein the metabolic syndrome is a liver steatosis.
8. The method of claim 6 , wherein the senolytic agent is a small molecule inhibitor.
9. The method of claim 6 , wherein the senolytic agent is a polynucleotide or oligonucleotide.
10. The method of claim 9 , wherein the polynucleotide or oligonucleotide is an antisense oligonucleotide, siRNA or shRNA.
11. The method of claim 8 , wherein the senolytic agent that is a small molecule inhibitor is administered to the subject in need thereof intermittently, wherein the intermittent administration is a treatment cycle followed by a non-treatment interval.
12. The method of claim 11 , wherein the non-treatment interval is between at least about 0.5 to 12 months.
13. The method of claim 9 , wherein the polynucleotide or oligonucleotide is administered to the subject in need thereof intermittently, wherein the intermittent administration is a treatment cycle followed by a non-treatment interval.
14. The method of claim 13 , wherein the non-treatment interval is between at least about 0.5 to 12 months.
15. A method of treating graft versus host disease in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising an effective amount of a senolytic agent that consists essentially of a Bcl-xL selective inhibitor.
16. The method of claim 15 , wherein the graft versus host disease is a result of a liver transplant.
17. The method of claim 15 , wherein the senolytic agent is a small molecule inhibitor.
18. The method of claim 15 , wherein the senolytic agent is a polynucleotide or oligonucleotide.
19. The method of claim 18 , wherein the polynucleotide or oligonucleotide is an antisense oligonucleotide, siRNA or shRNA.
20. The method of claim 17 , wherein the senolytic agent that is a small molecule inhibitor is administered to the subject in need thereof intermittently, wherein the intermittent administration is a treatment cycle followed by a non-treatment interval.
21. The method of claim 20 , wherein the non-treatment interval is between at least about 0.5 to 12 months.
22. The method of claim 18 , wherein the polynucleotide or oligonucleotide is administered to the subject in need thereof intermittently, wherein the intermittent administration is a treatment cycle followed by a non-treatment interval.
23. The method of claim 22 , wherein the non-treatment interval is between at least about 0.5 to 12 months.