The study investigates the impact of naturally occurring p16Ink4a-positive senescent cells on health and lifespan in mice. Using a transgenic mouse model (INK-ATTAC), researchers induced apoptosis in these cells by administering AP20187, a dimerizer that activates FKBP-fused Casp8. The results show that clearance of p16Ink4a-positive cells extended median lifespan in both male and female mice, delayed tumor formation, and attenuated age-related deterioration in multiple organs, including the kidney, heart, and fat. The clearance of these cells preserved organ function and prevented age-dependent changes such as glomerulosclerosis in the kidney and cardiac hypertrophy. The study suggests that p16Ink4a-positive cells negatively influence lifespan and healthspan by promoting tumor progression and age-related tissue dysfunction, and their therapeutic removal could be a promising approach to extend healthy lifespan.The study investigates the impact of naturally occurring p16Ink4a-positive senescent cells on health and lifespan in mice. Using a transgenic mouse model (INK-ATTAC), researchers induced apoptosis in these cells by administering AP20187, a dimerizer that activates FKBP-fused Casp8. The results show that clearance of p16Ink4a-positive cells extended median lifespan in both male and female mice, delayed tumor formation, and attenuated age-related deterioration in multiple organs, including the kidney, heart, and fat. The clearance of these cells preserved organ function and prevented age-dependent changes such as glomerulosclerosis in the kidney and cardiac hypertrophy. The study suggests that p16Ink4a-positive cells negatively influence lifespan and healthspan by promoting tumor progression and age-related tissue dysfunction, and their therapeutic removal could be a promising approach to extend healthy lifespan.