The administration of PKR or ISR antagonists after the full development of PVOD successfully restores PP1, inhibits the ISR, and alleviates PVOD symptoms in both young and aged rats, suggesting that pharmacological inhibition of the PKR/ISR axis is an effective strategy for mitigating advanced PVOD, irrespective of the patient’s age. The gene discussed is EIF2AK2; the disease is pulmonary venoocclusive disease.