Removing senescent cells from a mixed cell population or tissue using a phosphoinositide 3-kinase (PI3K) inhibitor

A method for selectively removing senescent cells from a target tissue in a subject in need thereof, comprising treating the subject according to a clinical protocol that includes:

• (1) a treatment period, during which senescent cells in the target tissue are contacted with an effective amount of a senolytic compound in one or more doses, wherein the amount of the senolytic compound is effective in reducing the number of senescent cells in the target tissue from a pre-treatment level to a post-treatment level;
• and
• (2) a subsequent non-treatment interval, during which further treatment with the senolytic compound is withheld from the subject;
• wherein the senolytic compound is a means for binding to and directly inhibiting phosphoinositide 3-kinase (PI3k),
• wherein the senescent cells are defined as p16 positive cells that are not cancer cells;
• wherein the duration of the non-treatment interval has been established as a time during which the number of senescent cells in the target tissue will remain below the pre-treatment level;
• and
• wherein the duration of the non-treatment interval is at least two weeks.

A method for reducing the number of senescent cells in a mixed cell population or tissue, comprising administering to the mixed cell population or tissue an effective amount of a senolytic compound,

• wherein the senescent cells are defined as p16 positive cells that are not cancer cells,
• wherein the senolytic compound is a means for binding to and directly inhibiting phosphoinositide 3-kinase (PI3k),
• wherein the mixed cell population or tissue is a population of cells cultured in vitro;
• and wherein the amount of the means for binding to and directly inhibiting PI3k is effective in promoting apoptosis in the p16-positive cells, thereby selectively removing at least some of the p16-positive cells from the mixed cell population or tissue.

A method for selectively removing senescent cells from a mixed cell population or tissue, comprising treating the mixed cell population or tissue with a treatment protocol that includes:

• (1) a treatment period, during which senescent cells in the mixed cell population or tissue are contacted with an effective amount of a senolytic compound in one or more doses, wherein the amount of the senolytic compound is effective in reducing the number of senescent cells in the mixed cell population or tissue from a pre-treatment level to a post-treatment level;
• and
• (2) a subsequent non-treatment interval, during which further treatment of the mixed cell population or tissue with the compound is withheld;
• wherein the senolytic compound is a means for binding to and directly inhibiting phosphoinositide 3-kinase (PI3k),
• wherein the senescent cells are defined as p16 positive cells that are not cancer cells,
• wherein the amount of the compound used during the treatment period is also effective in causing the number of senescent cells in the target tissue to remain below the pre-treatment level throughout the non-treatment interval;
• and
• wherein the duration of the non-treatment interval is at least two weeks.