Brain inflammation linked to aging : using Nothobranchius furzeri as a model ?

Aging is a progressive and physiological decline that among other phenotypes can lead to the decline in cognition and the progression of neurodegeneration. Chronic inflammation has been recognized as one of the hallmarks of age-related neurodegeneration along with the pro- and anti-inflammatory imbalance. Although inflammation is a natural defense mechanism, the response turns into chronic inflammation if its resolution is not achieved. During aging, this low-grade chronic inflammation is called “inflammaging” and is characterized by an increase in pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines. Inflammaging can occur in the brain through the modified secretion profile of cytokines by astrocytes and microglia, leading to neurodegenerative disorders. Fatty acids can act as immunomodulatory agents, for example, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid can produce eicosanoid mediators, which are involved in the inflammatory process. Punicic acid (PunA), an omega-5 isomer of conjugated linolenic acid (CLnA) with structural similarities to conjugated linoleic acid (CLA), is found in a great percentage in pomegranate seed oil (PSO) and was shown to have cytotoxic effects on HCT-116 and FaDu carcinoma cells. Additionally, PunA could be involved in the prevention of neurodegeneration through an increase of peroxisome proliferator-activated receptors (PPARs) and glucose transporter type 4 (GLUT4) expression. The aim of this work is to determine whether the expression of inflammation markers increases or decreases during aging in the brain, and under a specific diet (PunA supplementation through PSO-enriched Artemia) in a second experiment. Nothobranchius furzeri (GZR strain) was used as a model. N. furzeri is the fish with the shortest known lifespan in captivity and presents comparable molecular and cellular changes as well as aging phenotypes observed in humans with age. In this work, we measured the relative gene expression (RGE) of the pro-inflammatory cytokines; IL-6, IL-1β, TNF-α, and the immune regulators; TLR2 and APOA-I. The RGE of IL-1β significantly increased with age. Although age significantly impacted the RGE of IL-6, the trend was first a decline from six weeks of age followed by an incline from 20 weeks of age. In contrast, age did not appear to influence the RGE of TNF-α, TLR2, and APOA-I. The second experiment had to be stopped early due to potentially deleterious effect of PSO and/or PunA on the viability of N. furzeri.