Background: The gene FOXO3, encoding the transcription factor forkhead box O-3 (FoxO3), is one of only two for which genetic polymorphisms have exhibited consistent associations with longevity in diverse human populations. Objective: Here, we review the multitude of actions of FoxO3 that are relevant to health, and thus healthy ageing and longevity. Methods: The study involved a literature search for articles retrieved from PubMed using FoxO3 as keyword. Results: We review the molecular genetics of FOXO3 in longevity, then current knowledge of FoxO3 function relevant to ageing and lifespan. We describe how FoxOs are involved in energy metabolism, oxidative stress, proteostasis, apoptosis, cell cycle regulation, metabolic processes, immunity, inflammation and stem cell maintenance. The single FoxO in Hydra confers immortality to this fresh water polyp, but as more complex organisms evolved, this role has been usurped by the need for FoxO to control a broader range of specialized pathways across a wide spectrum of tissues assisted by the advent of as many as 4 FoxO subtypes in mammals. The major themes of FoxO3 are similar, but not identical, to other FoxOs and include regulation of cellular homeostasis, particularly of stem cells, and of inflammation, which is a common theme of age-related diseases. Other functions concern metabolism, cell cycle arrest, apoptosis, destruction of potentially damaging reactive oxygen species and proteostasis. Conclusions: The mechanism by which longevity-associated alleles of FOXO3 reduce age-related mortality is currently of great clinical interest. The prospect of optimizing FoxO3 activity in humans to increase lifespan and reduce age-related diseases represents an exciting avenue of clinical investigation. Research strategies directed at developing therapeutic agents that target FoxO3, its gene and proteins in the pathway(s) FoxO3 regulates should be encouraged and supported.

Spirulina microalgae contain a plethora of nutrient and non-nutrient molecules providing brain health benefits. Numerous in vivo evidence has provided support for the brain health potential of spirulina, highlighting antioxidant, anti-inflammatory, and neuroprotective mechanisms. Preliminary clinical studies have also suggested that spirulina can help to reduce mental fatigue, protect the vascular wall of brain vessels from endothelial damage and regulate internal pressure, thus contributing to the prevention and/or mitigating of cerebrovascular conditions. Furthermore, the use of spirulina in malnourished children appears to ameliorate motor, language, and cognitive skills, suggesting a reinforcing role in developmental mechanisms. Evidence of the central effect of spirulina on appetite regulation has also been shown. This review aims to understand the applicative potential of spirulina microalgae in the prevention and mitigation of brain disorders, highlighting the nutritional value of this “superfood”, and providing the current knowledge on relevant molecular mechanisms in the brain associated with its dietary introduction.

A steady increase in the elderly demographic, particularly those 85+ in age, has given rise to an elevation in global prevalence of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, and underscores an urgent need for novel, preventive, and disease-modifying strategies. Marine ecosystems represent a prolific source of bioactive compounds, among which xanthophyll carotenoids—oxygenated derivatives including astaxanthin, fucoxanthin, and canthaxanthin—have emerged as compelling candidates for neuroprotection. These compounds exhibit superior bioavailability and blood-brain barrier permeability compared to hydrocarbon carotenoids, attributed to their polar functional groups. Their potent bioactivity stems from a multifaceted ability to modulate core pathological processes: directly quenching reactive oxygen species, activating the Nrf2-mediated antioxidant response, inhibiting NF-κB-driven neuroinflammation, and interfering with the aggregation of toxic proteins like amyloid-β and α-synuclein. This review evaluates the preclinical and clinical evidence supporting the neuroprotective potential of these three marine xanthophylls. Astaxanthin demonstrates the most robust and extensive evidence base, from cellular models to human cognitive trials. Fucoxanthin shows parallel promise with unique effects on mitochondrial biogenesis, while canthaxanthin remains significantly understudied despite its strong antioxidant profile. We further discuss the translational challenges of bioavailability and formulation, highlighting innovative delivery systems, and propose future research directions to harness these marine-derived compounds for promoting brain health and mitigating age-related cognitive decline.