Krill oil protects dopaminergic neurons from age-related degeneration through temporal transcriptome rewiring and suppression of several hallmarks of aging

There is accumulating evidence that interfering with the basic aging mechanisms can enhance healthy longevity. Many cellular processes contribute to aging and are referred to as “hallmarks of aging”; by presumption, interventional/therapeutic strategies targeting on multiple ageing hallmarks could be more effective to delay ageing than targeting on one hallmark. While the health-promoting qualities of marine oils have been extensively studied, the underlying molecular mechanisms are not fully understood. Lipid extracts from Antarctic krill are rich in long-chain omega-3 fatty acids (eicosapentaenoic acid/EPA and docosahexaenoic acid/DHA), choline, and astaxanthin. Here, we investigated whether krill oil promotes healthy aging in the small roundworm C. elegans. We show that krill oil rewires distinct gene expression programs that contribute to attenuate several aging hallmarks, including oxidative stress, proteotoxic stress, senescence, genomic instability, and mitochondrial dysfunction. In a C. elegans model of Parkinson´s disease, krill oil protects dopaminergic neurons from aging-related degeneration, decreases alpha synuclein aggregation, and improves dopamine-dependent behavior and cognition. Mechanistically, krill oil increases neuronal resilience through temporal transcriptome rewiring to promote anti-oxidative stress and inflammation via healthspan regulating transcription factors such as SNK-1. However, also krill oil promotes DA neuron survival through regulation of synaptic transmission and neuronal functions via PBO-2 and RIM-1. Collectively, krill oil rewires global gene expression programs and promotes healthy aging via abrogating multiple ageing hallmarks, shedding light on further pre-clinical and clinical explorations. Overall design: Age synchronized wildtype and PD animals were grown on regular medium of medium supplemented with krill oil. These animals were harvested as day 1, day 3, day 6 adults and RNA isolation was performed the same day. Briefly, the animals were washed x2 with sterilized milliQ water, and collected in 1.5ml Eppendorf. The worm pellets were dispensed in 600 µl of TRI reagent or trizol and transferred to tube with sterile beads to homogenize the animals. From here RNA isolation for tissue was followed as described in the Direct-zol RNA Miniprep Kits protocol section. The isolated RNA was dissolved in 10 µl nuclease free water and the quality was analyzed in bioanalyser.