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Bay scallops are commercially important bivalve species for aquaculture worldwide, but the serious inbreeding depression is decreasing their production. Some interspecific hybrids of bay scallops (Argopecten irradians irradians) and Peruvian scallops (A. purpuratus) exhibit longer lifespan and significantly larger size for high yield, which may result from the longevity genes of Peruvian scallops. Insulin-like growth factor (IGF) system, as the conspicuous entry point of insulin/insulin-like growth factor signal (IIS) pathway, regulates various cellular processes including growth, autophagy, aging and longevity, but its roles remain unexplored in marine animals. In this study, we separately cloned a unique IGF2 (ApIGF2 and AiIGF2) and IGF1R (ApIGF1R and AiIGF1R) for the first time from two closely related Argopecten scallops with distinct lifespans and characterized for their ability to regulate longevity. Sequence analysis demonstrated that there were six-span transmembrane domains located at the additional extension of C-terminus special to AiIGF2, which appeared to relate to the differences in posttranslational processing. The amino acid variation (Y247) in TyrKc domain may be a key site affecting ApIGF1R kinase activity for longevity. Spatiotemporal expression of IGF2 and IGF1R during development and aging showed that the mantle and gonad are representative tissues for aging in scallops. The dietary restriction assay revealed the beneficial effects of attenuated IGF2 and IGF1R levels on longevity in scallops. The invigorated IGF1R conferred DNA repair and prosurvival properties to Peruvian scallops for radio-resistance after acute radioresistance. Inhibition of AiIGF1R upregulated the expression of senescence-associated genes (PENT, FoxO, CAT, Mn-SOD) and antioxidant enzyme activities, and suppressed the senescence marker β-GAL activity, indicating that IGF1R was a crucial regulator for longevity in scallops. Collectively, our work would bring us closer to understanding the longevity mechanism mediated by IGF system and breeding larger and long-lived hybrids for the sustainable development of aquaculture.

Dual specificity mitogen-activated protein kinase kinase 1 (MEK1) has been found to regulate aging through the Ras/Raf/MEK/ERK cascade in terrestrial animals. However, few reports have focused on MEK1 promoting aging in marine bivalves. In this study, we aimed to examine the potential roles of MEK1 in the regulation of aging in two Argopecten scallops, the bay scallop A. irradians and the Peruvian scallop A. purpuratus, which are closely related but with distinct lifespan. The complete ORFs of AiiMEK1 and ApuMEK1 were both 1209 bp, encoding 403 identical amino acids but with 41 synonymous SNPs, which may have contributed to the different activities of MEK1 in two scallops. Nutrient restriction, one of the most effective non-genetic means of promoting life span, significantly inhibit the expression of AiiMEK1 and ApuMEK1. The response in hepatopancreas of A. irradians to nutrient restriction was more persistently than that in A. purpuratus. RNAi of AiiMEK1 significantly increased the expression of its downstream genes known to favor longevity, such as FoxO and SOD, while decreased the expression of ERK1/2 and the key genes in the mTOR signaling pathway, as well as the β-GAL activity (a marker for senescence). These results indicated that AiiMEK1 may play a negative role in longevity through Ras/Raf/MEK/ERK pathway. Our results may provide new perspective for understanding of the conservative functions of MEK1 in regulation of aging in animals and benefit the genetic selection of scallops.

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) has been found to regulate longevity through the PI3K/Akt/FoxO pathway and maintenance of genome integrity in worms, flies, and mammals. However, limited information is available on the roles of PTEN in longevity of aquatic animals. Here we extended this paradigm using two closely related Argopecten scallops, Argopecten purpuratus, and Argopecten irradians, with significantly distinct life spans, which are commercially important bivalve species for fishery and aquaculture in China, United States, Peru, and Chile. The ORFs of the ApPTEN and AiPTEN were 1,476 and 1,473 bp, which encoded 491 and 490 amino acids, respectively. There were 48 synonymous and 16 non-synonymous SNPs and one InDel of three nucleotides between ApPTEN and AiPTEN, resulting in variations in 15 amino acids and lack of S453 in AiPTEN. Differences in conformation and posttranslational modification were predicted between ApPTEN and AiPTEN, which may indicate different activities of ApPTEN and AiPTEN. When the animals were subjected to nutrition restriction, the expression of both ApPTEN and AiPTEN was upregulated, with AiPTEN responded faster and more robust than ApPTEN. Ionizing radiation induced significantly elevated expression of ApPTNE but not AiPTEN in the adductor muscle, and the mortality rate of A. purpuratus was significantly lower than that of A. irradians, indicating that ApPTNE may play a protective role by maintaining the genome integrity. RNAi of ApPTNE significantly downregulated the expression of its downstream regulated genes known to favor longevity, such as FoxO, Mn-SOD, and CAT. These results indicated that PTEN may contribute to the longevity of A. purpuratus through regulation of nutrient availability and genomic stability, probably via PI3K/Akt/FoxO pathway. Our study may provide new evidence for understanding of the conservative functions of PTEN in regulation of lifespan in animals and human, and it may also benefit the selection of scallops strains with long lifespan and thus larger size. [ABSTRACT FROM AUTHOR]

Plant resistance against insects mainly depends on nutrient restriction and toxic metabolites, but the relative importance of nutrition and toxins remains elusive. We examined performance, nutrition ingestion, and transcriptome response of the English grain aphid, Sitobion avenae, feeding on resistant Xiaoyan 22 (XY22) and susceptible Xinong 979 (XN979) wheat cultivars. Aphids had lower body weight and fecundity when feeding on XY22 than on XN979, although the phloem sap of XY22 had a higher nutritive quality (in terms of amino acid:sucrose ratio). Aphids feeding on XY22 also had a lower honeydew excretion rate than those on XN979, suggesting that aphids ingested less phloem sap from XY22. The transcriptome data showed 600 differentially expressed genes (DEGs), and 11 of the top 20 KEGG pathways significantly enriched in DEGs were involved in nutrient metabolism. We found 81 DEGs associated with the metabolism of sugars, lipids, and amino acids, 59 of which were significantly downregulated in aphids feeding on XY22. In contrast, there were 18 DEGs related to detoxifying metabolism, namely eight UDP-glucuronosyltransferases, six cytochromes P450 monooxygenases, one glutathione S-transferase, two ATP-binding cassette transporters, and one major facilitator superfamily transporter; 12 of these were upregulated in the aphids feeding on XY22. Our results indicated that both the quantity and quality of phloem nutrition available to aphids are critical for the growth and development of aphids, and the higher resistance of XY22 is mainly due to the reduction in phloem sap ingested by aphids, rather than toxic metabolites.

Scope: Grifola frondosa has been shown to induce immune modulatory, modulate autophagy, and apoptosis in cancer cells. However, little is known about its potential for managing tumor progression as an adjunct to nutrient restriction., Methods and Results: Water extract produces a G. frondosa polysaccharide-protein complex (G. frondosa PPC) of average molecular weight of 46.48 kDa, with glucose (54.8%) as the main constituent. Under serum-restricted conditions, G. frondosa PPC can significantly inhibit MC38 colorectal tumor cell migration in vitro. Under alternate-day fasting condition, G. frondosa PPC can only significantly inhibit the growth of subcutaneous (s.c.) tumor, but is feeble in halting its spread in the intraperitoneal (i.p.) cavity in tumor-bearing mice. Histopathological examination and Raman imaging show a significant increase in lipid content in the tumor microenvironment (TME) tissue of the s.c. tumor-bearing mice. G. frondosa PPC significantly increases C17:0 and C24:0 saturated fatty acids and significantly decreases C16:1 and C18:1 monounsaturated fatty acids in the TME of s.c. tumor-bearing mice compared with the i.p. cavity model., Conclusion: G. frondosa PPC significantly inhibits tumor growth in s.c. tumor-bearing mice under intermittent fasting conditions by altering the fatty acid composition of the TME., (© 2024 Wiley‐VCH GmbH.)

Background: Drosophila neuroblasts (NBs) are neural stem cells whose maintenance relies on Notch activity. NBs proliferate throughout larval stages to generate a large number of adult neurons. Their proliferation is protected under conditions of nutrition restriction but the mechanisms responsible are not fully understood. As amino acid transporters (Solute Carrier transporters, SLCs), such as SLC36, have important roles in coupling nutrition inputs to growth pathways, they may have a role in this process. For example, an SLC36 family transporter Pathetic (Path) that supports body size and neural dendrite growth in Drosophila, was identified as a putative Notch target in genome-wide studies. However, its role in sustaining stem cell proliferation and maintenance has not been investigated. This study aimed to investigate the function of Path in the larval NBs and to determine whether it is involved in protecting them from nutrient deprivation. Methods: The expression and regulation of Path in the Drosophila larval brain was analysed using a GFP knock-in allele and reporter genes containing putative Notch regulated enhancers. Path function in NB proliferation and overall brain growth was investigated under different nutrition conditions by depleting it from specific cell types in the CNS, using mitotic recombination to generate mutant clones or by directed RNA-interference. Results: Path is expressed in both NBs and glial cells in the Drosophila CNS. In NBs, path is directly targeted by Notch signalling via Su(H) binding at an intronic enhancer, PathNRE. This enhancer is responsive to Notch regulation both in cell lines and in vivo. Loss of path in neural stem cells delayed proliferation, consistent with it having a role in NB maintenance. Expression from pathNRE was compromised in conditions of amino acid deprivation although other Notch regulated enhancers are unaffected. However, NB-expressed Path was not required for brain sparing under amino acid deprivation. Instead, it appears that Path is important in glial cells to help protect brain growth under conditions of nutrient restriction. Conclusions: We identify a novel Notch target gene path that is required in NBs for neural stem cell proliferation, while in glia it protects brain growth under nutrition restriction. [ABSTRACT FROM AUTHOR]

Nutrition is an important factor that regulates reproductive performance of sheep and affects follicle development. However, the correlation between nutrition and follicle development is poorly understood at the molecular level. To study its possible molecular mechanisms, we performed expression profiling of granulosa cells isolated from sheep that were fed different levels of nutrition levels during the luteal phase. To do this, ewes received a maintenance diet (M), and their estrus was synchronized by intravaginal progestogen sponges for 12 days. Ewes were randomly divided into the short-term dietary-restricted group (R; 0.5 × M) and the nutrient-supplemented group (S; 1.5 × M). RNA samples were extracted from granulosa cells. Transcriptome libraries from each group were constructed by Illumina sequencing. Among 18 468 detected genes, 170 genes were significantly differentially expressed, of which 140 genes were upregulated and 30 genes were downregulated in group S relative to group R. These genes could be candidates regulating follicular development in sheep. Gene Ontology, KEGG and clustering analyses were performed. Genes related to oocyte meiosis, such as ADCY7, were upregulated. We identified two important groups of related genes that were upregulated with improved nutrition: one group comprising the genes PTGS2, UCP2 and steroidogenic acute regulatory protein and the other group comprising interleukin-1A and interleukin-1B. The genes within each group showed similar expression patterns. Additionally, all five genes are involved in the reproduction process. Quantitative real-time PCR was performed to validate the results of expression profiling. These data in our study are an abundant genomic resource to expand the understanding of the molecular and cellular events underlying follicle development. [ABSTRACT FROM AUTHOR]

Abstract: Maternal nutrient restriction during pregnancy is associated with the development of a “thrifty phenotype” in offspring, conferring increased prevalence of metabolic diseases in adulthood. To explore the possible mechanisms behind heart diseases in adulthood following maternal nutrient restriction, dams were fed a nutrient-restricted (NR: 50%) or control (100%) diet from 28 to 78 days of gestation. Both groups were then fed 100% of requirements to lambing. At 6 years of age, female offspring of NR and control ewes of similar weight and body condition were subjected to ad libitum feeding of a highly palatable diet for 12 weeks. Cardiac geometry, post-insulin receptor signaling, autophagy and proinflammatory cytokines were evaluated in hearts from adult offspring. Our results indicated that maternal nutrient restriction overtly increased body weight gain and triggered cardiac remodeling in offspring following the 12-week ad libitum feeding. Phosphorylation of insulin receptor substrate-1 (IRS1) was increased in left but not right ventricles from NR offspring. Levels of signal transducer and activator of transcription-3 were up-regulated in left ventricles, whereas expression of tumor necrosis factor-α and toll-like receptor-4 was enhanced in right ventricles, in adult offspring of maternal nutrition-restricted ewes. No significant differences were found in pan-IRS1, pan-AMP-dependent protein kinase (AMPK), pan-Akt, phosphorylated AMPK, phosphorylated Akt, glucose transporter 4, phosphorylated mammalian target of rapamycin, Beclin-1 and microtubule-associated protein 1 light-chain 3 II proteins in left and right ventricles between the control and NR offspring. These data revealed that maternal nutrient restriction during early to mid gestation may predispose adult offspring to cardiac remodeling possibly associated with phosphorylation of IRS1 as well as proinflammatory cytokines but not autophagy. [Copyright &y& Elsevier]

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) has been found to regulate longevity through the PI3K/Akt/FoxO pathway and maintenance of genome integrity in worms, flies, and mammals. However, limited information is available on the roles of PTEN in longevity of aquatic animals. Here we extended this paradigm using two closely related Argopecten scallops, Argopecten purpuratus , and Argopecten irradians , with significantly distinct life spans, which are commercially important bivalve species for fishery and aquaculture in China, United States, Peru, and Chile. The ORFs of the ApPTEN and AiPTEN were 1,476 and 1,473 bp, which encoded 491 and 490 amino acids, respectively. There were 48 synonymous and 16 non-synonymous SNPs and one InDel of three nucleotides between ApPTEN and AiPTEN , resulting in variations in 15 amino acids and lack of S453 in AiPTEN. Differences in conformation and posttranslational modification were predicted between ApPTEN and AiPTEN, which may indicate different activities of ApPTEN and AiPTEN. When the animals were subjected to nutrition restriction, the expression of both ApPTEN and AiPTEN was upregulated, with AiPTEN responded faster and more robust than ApPTEN . Ionizing radiation induced significantly elevated expression of ApPTNE but not AiPTEN in the adductor muscle, and the mortality rate of A. purpuratus was significantly lower than that of A. irradians , indicating that ApPTNE may play a protective role by maintaining the genome integrity. RNAi of ApPTNE significantly downregulated the expression of its downstream regulated genes known to favor longevity, such as FoxO , Mn-SOD , and CAT . These results indicated that PTEN may contribute to the longevity of A. purpuratus through regulation of nutrient availability and genomic stability, probably via PI3K/Akt/FoxO pathway. Our study may provide new evidence for understanding of the conservative functions of PTEN in regulation of lifespan in animals and human, and it may also benefit the selection of scallops strains with long lifespan and thus larger size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Lu, Wang, Ning, Chen, Wang and Yuan.)

Abstract: For placental transmission of scrapie to occur, the normal cellular prion protein (PrPC) must be converted to an abnormal infectious form known as PrPSc. PrPC genotype influences susceptibility to contracting scrapie, but we still do not understand whether genotype or expression levels of PrPC are important in transmission of scrapie. Some evidence exists that nutrition affects expression levels of PrPC. Thus, we evaluated the effects of genotype and nutrition on PrPC mRNA and protein expression in adolescent ewes fed at control (100% of National Research Council [NRC] requirements) or restricted (60% of NRC) levels of diet intake during two periods of pregnancy (days 50–90 and days 90–130)]. Gravid uteri (n =50) from singleton pregnancies were collected at day 130, and placentomes were either separated into caruncular (CAR; maternal) or cotyledonary (COT; fetal) placenta and snap-frozen for PrPC mRNA expression or perfusion fixed for PrPC protein expression. PrPC genotypes were determined (codons 136 and 171) using SNP assay. There were no genotype effects on PrPC mRNA expression in CAR or on PrPC protein expression in either CAR or COT, but PrPC mRNA expression in COT was greater (P <0.02) when codon 136 was homozygous for alanine. Some PrPC protein-positive cells were found in the epithelium of CAR, but most were found in trophoblast binucleate and mononucleate cells of COT. In CAR, from days 90 to 130, PrPC protein abundance was greater (P =0.003) in diet-restricted ewes than in control ewes, but was less uniformly distributed (P <0.007). Additionally, in COT, from days 90 to 130, PrPC protein was less uniformly distributed (P <0.01) in diet-restricted ewes. The localized increase in PrPC protein expression, found in ewes diet-restricted late in pregnancy, may suggest a protective role for PrPC in placental biology. Further study is needed to evaluate whether nutrition, PrPC genotype, and PrPC expression levels influence placental transmission of scrapie. [Copyright &y& Elsevier]