The study investigates the role of cellular senescence in aging and age-related disorders by targeting p16Ink4a-positive senescent cells. The researchers developed a novel transgenic strategy, INK-ATTAC, which allows for the inducible elimination of these cells using a drug. In a progeroid mouse model (BubR1^JHH), the INK-ATTAC transgene was shown to effectively remove p16Ink4a-positive senescent cells upon drug treatment. This clearance delayed the onset and progression of age-related phenotypes in tissues such as adipose tissue, skeletal muscle, and the eye. The results indicate that cellular senescence is causally linked to age-related dysfunction, and removing senescent cells can prevent or delay tissue dysfunction, potentially extending healthy lifespan. The study also found no significant side effects of senescent cell clearance, suggesting that therapeutic interventions targeting senescent cells could be a promising approach to treating or delaying age-related diseases.The study investigates the role of cellular senescence in aging and age-related disorders by targeting p16Ink4a-positive senescent cells. The researchers developed a novel transgenic strategy, INK-ATTAC, which allows for the inducible elimination of these cells using a drug. In a progeroid mouse model (BubR1^JHH), the INK-ATTAC transgene was shown to effectively remove p16Ink4a-positive senescent cells upon drug treatment. This clearance delayed the onset and progression of age-related phenotypes in tissues such as adipose tissue, skeletal muscle, and the eye. The results indicate that cellular senescence is causally linked to age-related dysfunction, and removing senescent cells can prevent or delay tissue dysfunction, potentially extending healthy lifespan. The study also found no significant side effects of senescent cell clearance, suggesting that therapeutic interventions targeting senescent cells could be a promising approach to treating or delaying age-related diseases.