Obesity is associated with cardiopulmonary diseases. Despite Obesity and aging converging in similar pathways, specifically inflammation-associated genomic instability, their interdependency remains unclear. We recently demonstrated that perinatal obesity triggers bronchial/vascular remodeling through Interleukin 6 (IL-6). We investigated if and how perinatal obesity induces early genomic instability in alveolar epithelial cells type 2 (AT2) leading to alveolar simplification. Lungs of offspring of high-fat diet- or standard-diet-fed dams were analyzed at postnatal day 21 (P21), P70, P365 and after 1.5years, including global and AT2-specific transcriptomic and epigenetic profiling. Cultured AT2, precision-cut lung slices and bronchioalveolar lung organoids were used for ex vivo studies. Perinatal obesity induced a life-long emphysema-like lung structure with a reduction of AT2, increased DDR (?H2AX+) and senescence (p21+). Global and AT2-specific RNA-Seq together with AT2-specific ATAC-Seq identified DNA damage and repair processes together with transcriptional stress and aging-associated pathways after perinatal obesity. Cultured AT2, PCLS and BALOs demonstrated that WAT secretome inhibits growth and induces DDR, senescence and loss of AT2 through IL-6. IL-6 null mice and mice with pharmacological inhibition of IL-6 signaling were protected from DDR and alveolar growth arrest after perinatal obesity. Finally, human lungs with emphysema showed increased DDR and AT2 loss. Our data demonstrate that perinatal obesity induces genomic instability in AT2 with life-long emphysema-like lung structure, a process that is in part mediated by WAT derived IL-6.