Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging.

Although the human lifespan has increased in the past century owing to advances in medicine and lifestyle, the human healthspan has not kept up the same pace, especially in brain aging. Consequently, the role of preventive health interventions has become a crucial strategy, in particular, the identification of nutritional compounds that could alleviate the deleterious effects of aging. Among nutrients to cope with aging in special cognitive decline, the long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have emerged as very promising ones. Due to their neuroinflammatory resolving effects, an increased status of DHA and EPA in the elderly has been linked to better cognitive function and a lower risk of dementia. However, the results from clinical studies do not show consistent evidence and intake recommendations for old adults are lacking. Recently, supplementation with structured forms of EPA and DHA, which can be derived natural forms or targeted structures, have proven enhanced bioavailability and powerful benefits. This review summarizes present and future perspectives of new structures of ω-3 LCPUFAs and the role of "omic" technologies combined with the use of high-throughput in vivo models to shed light on the relationships and underlying mechanisms between ω-3 LCPUFAs and healthy aging.

Emerging models for studying adipose tissue metabolism.

Understanding adipose metabolism is essential for addressing obesity and related health concerns. However, the ethical and scientific pressure to animal testing, aligning with the 3Rs, has triggered the implementation of diverse alternative models for analysing anomalies in adipose metabolism. In this review, we will address this issue from various perspectives. Traditional adipocyte cell cultures, whether animal or human-derived, offer a fundamental starting point. These systems have their merits but may not fully replicate in vivo complexity. Established cell lines are valuable for high-throughput screening but may lack the authenticity of primary-derived adipocytes, which closely mimic native tissue. To enhance model sophistication, spheroids have been introduced. These three-dimensional cultures better mimicking the in vivo microenvironment, enabling the study of intricate cell-cell interactions, gene expression, and metabolic pathways. Organ-on-a-chip (OoC) platforms take this further by integrating multiple cell types into microfluidic devices, simulating tissue-level functions. Adipose-OoC (AOoC) provides dynamic environments with applications spanning drug testing to personalized medicine and nutrition. Beyond in vitro models, genetically amenable organisms (Caenorhabditis elegans, Drosophila melanogaster, and zebrafish larvae) have become powerful tools for investigating fundamental molecular mechanisms that govern adipose tissue functions. Their genetic tractability allows for efficient manipulation and high-throughput studies. In conclusion, a diverse array of research models is crucial for deciphering adipose metabolism. By leveraging traditional adipocyte cell cultures, primary-derived cells, spheroids, AOoCs, and lower organism models, we bridge the gap between animal testing and a more ethical, scientifically robust, and human-relevant approach, advancing our understanding of adipose tissue metabolism and its impact on health.

Exploring Metabolic and Gut Microbiome Responses to Paraquat Administration in Male Wistar Rats: Implications for Oxidative Stress.

In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; 1H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., Escherichia coli and Akkermansia muciniphila) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.

Structured Docosahexaenoic Acid (DHA) Enhances Motility and Promotes the Antioxidant Capacity of Aged C. elegans.

The human lifespan has increased over the past century; however, healthspans have not kept up with this trend, especially cognitive health. Among nutrients for brain function maintenance, long-chain omega-3 polyunsaturated fatty acids (ω-3 LCPUFA): DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) must be highlighted, particularly structured forms of EPA and DHA which were developed to improve bioavailability and bioactivity in comparison with conventional ω-3 supplements. This study aims to elucidate the effect of a structured triglyceride form of DHA (DHA-TG) on the healthspan of aged C. elegans. Using a thrashing assay, the nematodes were monitored at 4, 8, and 12 days of adulthood, and DHA-TG improved its motility at every age without affecting lifespan. In addition, the treatment promoted antioxidant capacity by enhancing the activity and expression of SOD (superoxide dismutase) in the nematodes. Lastly, as the effect of DHA-TG was lost in the DAF-16 mutant strain, it might be hypothesized that the effects of DHA need DAF-16/FOXO as an intermediary. In brief, DHA-TG exerted a healthspan-promoting effect resulting in both enhanced physical fitness and increased antioxidant defense in aged C. elegans. For the first time, an improvement in locomotive function in aged wild-type nematodes is described following DHA-TG treatment.