The ETERNITY project is advancing the understanding of how metabolic dysfunction contributes to aging and age-related disorders. Research on brain energy metabolism has provided key insights into the metabolic regulation of neurons and microglia, revealing sex-specific adaptations and mitochondrial dynamics in response to diet and aging.
Further efforts have focused on identifying metabolic pathways altered after synaptic stimulation in vitro and in vivo, paving the way for future experiments in Alzheimer’s disease models. These studies aim to characterize metabolic disruptions and assess their potential as therapeutic targets. In parallel, the project has made significant progress in developing interventional strategies for age-related metabolic dysfunctions. A novel CAR-T cell system targeting senescent cells demonstrated selective cytotoxicity, presenting a promising senotherapeutic approach. A surfaceome analysis also identified unique surface proteins in senescent cells as potential therapeutic targets.
Long-term in vivo studies have explored diet-based interventions, comparing ad libitum and time-restricted feeding under standard or high-fat diet conditions. Findings suggest that time-restricted feeding preserves cognitive function during senescence, independent of diet, and improves glucose metabolism, even surpassing control diet groups. Furthermore, analysis of metabolic markers revealed shifts in ketone metabolism and fatty acid oxidation-related gene expression patterns, confirming diet-induced metabolic adaptations.
The outcomes of the ETERNITY project have strong translational potential, offering novel therapeutic targets and dietary interventions to mitigate cognitive decline and metabolic dysfunction in aging and neurodegenerative diseases. Further research will focus on validating metabolic targets in preclinical neurodegeneration models, expanding interventional strategies, and identifying potential human biomarkers for early detection and personalized treatments. Regulatory and commercialization pathways will also be explored, including patent protection for potential drug targets and collaborations with the pharmaceutical and nutraceutical industries. International partnerships will be sought to advance clinical validation and ensure the successful translation of findings into real-world applications.
By integrating fundamental research with translational applications, the ETERNITY project is poised to contribute significantly to the fight against neurodegeneration and to foster the development of innovative therapeutic solutions for aging populations.
