Transgenic mouse having a transgene that converts a prodrug into a cytotoxic compound in senescent cells

A mouse from a strain of mice having a transgene inserted in their genome, the transgene containing:

• a p16INK4a promoter sequence;
• a nucleotide sequence encoding an enzyme that converts a prodrug to a cytotoxic agent, wherein the enzyme is expressed under control of the p16INK4a promoter so as to be produced by senescent cells in the mouse;
• and
• a nucleotide sequence containing a luminescent and/or a fluorescent marker protein, expressed under control of the p16INK4a promoter so as to be produced by senescent cells in the mouse;
• wherein treating the mouse with the prodrug results in the enzyme converting the prodrug to the cytotoxic agent in senescent cells, thereby killing the senescent cells but killing less than 10% of non-senescent cells;
• whereby progression of an age-related disorder or an age-sensitive trait is delayed in the mouse treated with the prodrug compared with an untreated mouse of the same strain.

A method for removing senescent cells from a tissue, comprising contacting the senescent cells with a prodrug,

• wherein the genome of cells in the tissue contains a recombinant polynucleotide in which a p16INK4a promoter sequence controls expression of an enzyme so as to cause the enzyme to be expressed in senescent cells;
• wherein the enzyme converts the prodrug to a cytotoxic agent;
• wherein contacting the senescent cells with the prodrug results in the prodrug being converted to the cytotoxic agent by the enzyme expressed from the recombinant polynucleotide in the senescent cells, thereby killing the senescent cells but killing less than 10% of non-senescent cells in the tissue;
• whereby progression of an age-related disorder or an age-sensitive trait is delayed in the tissue as a result of contacting the senescent cells in the tissue with the prodrug.