The causal role of senescence on impaired energy homeostasis is demonstrated by targeting senescent cells with drug‐inducible “suicide” genes driven by the p16(Ink4a; Palmer, Xu, et al., 2019) or p21 (Wang et al., 2022) promoter or by senolytic drugs in obese and aged mice, strategies associated with reduction of age‐ and obesity‐related metabolic abnormalities. Here, CDKN2A is linked to obesity due to melanocortin 4 receptor deficiency.