Potential roles of LMNA in promoting longevity for larger Argopecten scallops

Bay scallops, Argopecten irradians, are a commercial bivalve species, but their small size, short longevity, and serious inbreeding depression make it difficult to further promote the farming of this species. Compared with bay scallops, some interspecific hybrids bay scallops and Peruvian scallops (A. purpuratus) have extraordinary growth advantages, such as longer longevity and greater sizes, which can be attributed to the longevity genes of Peruvian scallops (7–10 years). Lamin A/C (LMNA) is a nuclear scaffold protein that interacts with specific histone deacetylases (HDAC) to maintain their activity and regulate gene expression. LMNA mutations can lead to premature aging, and altered levels of LMNA are found in diverse diseases in most vertebrates; however, its roles in regulating senescence remains largely unknown in mollusk species. In this study, we cloned LMNA open reading frames (ORFs) from two closely correlated Argopecten scallops with different lifespans and explored their capacity to modulate longevity. One hundred and twenty-eight variations and one InDel of three nucleotides were discovered in ApLMNA and AiLMNA at the nucleotide sequence level, with 109 synonymous and 19 non-synonymous SNPs, leading to 16 amino acid variations and the absence of S16 in AiLMNA. Tissue distribution analysis revealed that these two genes exhibited different trends during the development and aging of the two scallops. A yeast two-hybrid assays revealed a stronger interaction between LMNA and SIRT1 in A. purpuratus than in A. irradians. RNA interference (RNAi) of ApLMNA at 6 h significantly upregulated the expression of its downstream gene, SIRT1; however, SIRT1 was downregulated after RNAi of AiLMNA. The SIRT1-targeted genes FoxO, Mn-SOD, and CAT also showed different expression patterns. Transcriptome analysis revealed that the longevity pathways in Peruvian scallops were activated after RNAi. Overall, our study provides interesting avenues to understand the mechanism of longevity through LMNA genes and will help produce long-lived and large crossbred offsprings to maintain fisheries and aquaculture going.