Nutrient restriction (NR) extends lifespan in many species. High latitudes are characterized by cold-water temperature and food limitations, where bivalves may mimic NR like vertebrates, which could result in a prolonged life expectancy. The long-lived Peruvian scallop (7-10 years) distributes naturally at relatively higher latitudes than the annual bay scallop. However, the relationship and the mechanism underlying the food availability and lifespan are unclear in bivalves. In this study, the genetic response to NR was first investigated in bivalves with distinct lifespans. Peruvian scallops persistently responded to NR mainly via metabolic pathways, but that began to play roles in bay scallops after 56 days. Significant down-regulated expression of long-chain saturated fatty acid synthetase in both two scallops and increased expression of SCD5 and LIPN2 in Peruvian scallops might contribute to MUFA accumulation under NR. SOD1 was more highly expressed in Peruvian scallops than in bay scallops under NR, and strong autophagy was detected only in Peruvian scallops. Peruvian scallops presented much lower MDA levels and higher SOD1 activities than bay scallops. These findings help us understanding the role of lipases and antioxidases in longevity of bivalves, and provided potential biomarkers for breeding long-lived larger scallops.