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.

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.

Background: Oral supplementation with omega‐3 polyunsaturated fatty acids (ω‐3 PUFAs) has shown beneficial effects in some dermatologic diseases (i.e., atopic dermatitis, acne, psoriasis, burns), but the actual effect of local application of ω‐3 PUFAs for improving skin health is still under investigation.Aims: This paper systematically reviewed the current articles regarding the use of topical ω‐3 PUFAs in the treatment of skin diseases to evaluate its efficacy and safety.Methods: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) recommendations. Studies in which ω‐3 PUFAs were administered as oral treatments, those with a reduced or unknown ω‐3 PUFAs composition, and those using with skin fish grafts were excluded.Results: In skin models of psoriasis, wounds, dermatitis, and melanoma, topical ω‐3 PUFAs showed an overall beneficial effect associated with the anti‐inflammatory properties of these compounds. Furthermore, none of the studies reported cases of skin irritation, cytotoxicity, or any adverse events.Conclusions: The increasing number of studies conducted on topical treatments with ω‐3 PUFAs and the existing evidence suggest that ω‐3 PUFAs could be a promising option as an adjuvant or complementary treatment in managing several dermatological conditions. However, there is still a lack of consensus about the optimal dosage, molecules, or delivery methods of ω‐3 PUFAs; consequently, more clinical studies are needed.

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.

A common hallmark of neurodegenerative diseases is the accumulation of polypeptide aggregates in neurons. Despite the primary cause of these diseases being inherently genetic, their development can be delayed with proper preventive treatments. Long-chain polyunsaturated fatty acids (ω-3 LCPUFA) are promising bioactive nutrients that are beneficial for brain health. In this study, the impact of an oil rich in a structured form of docosahexaenoic acid (DHA) triglyceride (TG) was assessed in a Caenorhabditis elegans model expressing long poly-glutamine (polyQ) chains, which mimics the symptomatology of polyQ-related neurodegenerative diseases such as Huntington’s disease (HD), among others. The lifespan, the motility, the number of polyQ aggregates, the oxidative stress resistance, and the cognitive performance associated with sensitive stimuli was measured in mutant nematodes with polyQ aggregates. Overall, DHA-TG at 0.5 µM improved the lifespan, the motility, the oxidative stress resistance, and the cognitive performance of the nematodes, emphasizing the protection against serotonergic synapse dysfunction. Furthermore, the treatment reduced the polyQ aggregates in the nematodes. The data described herein shed light on the connection between DHA and the cognitive performance in neurodegenerative diseases and demonstrated the potential of DHA-TG as nutritional co-adjuvant to prevent the development of polyQ-associated dysfunctions.