Life Span Is Prolonged in Food-Restricted Autoimmune-Prone (NZB × NZW)F(1) Mice Fed a Diet Enriched with (n-3) Fatty Acids

Abstract

Moderate food and/or energy (calorie) restriction delays age-related immune dysfunction and prolongs life span in multiple animal models. The amount and type of dietary fatty acids can also profoundly affect life span. Marine-derived fish oils contain (n-3) fatty acids, which have potent anti-inflammatory properties. We therefore examined the influence of food restriction (40% overall reduction in intake of all dietary components) combined with substitution of fish oil for corn oil in a factorial design. Autoimmune-prone (NZB x NZW)F(1) (B/W) mice, which develop fatal autoimmune renal disease, were used. The food-restricted/fish oil diet maximally extended median life span to 645 d (vs. 494 d for the food-restricted corn oil diet). Similarly, fish oil prolonged life span in the ad libitum-fed mice to 345 d (vs. 242 for the ad libitum/corn oil diet). Increased life span was partially associated with decreased body weight, blunting renal proinflammatory cytokine (interferon-gamma, interleukins-10 and -12 and tumor necrosis factor-alpha) levels and lower nuclear factor-kappaB (NF-kappaB). Reductions in NF-kappaB were preceded by enhanced superoxide dismutase, catalase and glutathione peroxidase activities. These findings demonstrate the profound additive effects of food restriction and (n-3) fatty acids in prolonging life span in B/W mice. These observations may have additional implications in the management of obesity, diabetes, cancer and/or the aging process.

Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer

“…Although no previous studies of the effects of FO on lifespan of long‐lived strains of mice have been reported, several studies have been reported in which omega‐3 fatty acids increased lifespan in short‐lived autoimmune‐prone (NZB × NZW)F1 mice (Jolly et al ., 2001; Fernandes, 2008). A demographic analysis of the survival of fish oil‐fed (NZBxNZW)F(1) mice by de Magalhaes et al .…”

Synergistic induction of lipid catabolism and anti-inflammatory lipids in white fat of dietary obese mice in response to calorie restriction and n-3 fatty acids

“…Importantly, LC n-3 PUFA also decrease inflammation [14], including obesity-associated low-grade inflammation of WAT [15,16], characterised by altered secretion patterns of adipokines, which contributes to insulin resistance [1]. The anti-inflammatory effects of LC n-3 PUFA probably depend on the formation of their active metabolites.…”

Effect of Life-Long Dietary <i>n</i>-6/<i>n</i>-3 Fatty Acid Ratio on Life Span, Serum Lipids and Serum Glucose in Wistar Rats

“…Du et al observed that the life span of mice fed a DHA-rich diet was longer than that of mice fed a lard diet abundant in saturated fatty acids and a safflower oil diet rich in linoleic acid (11), while Jolly et al reported that the life span of a mouse autoimmune model was prolonged in a group fed n-3 fatty acid-rich fish oil, compared to that in a group fed a corn diet (12). However, it has also been reported that the life spans of BHE/cdb rats (a rat non-obese NIDDM and hyperlipidemia model) and senescence-accelerated mice were shorter in animals fed an n-3 fatty acid-rich diet than in those fed a linoleic acid-rich safflower oil diet (13,14).…”

“…Dietary lipid type-associated variations in the rat and mouse life span have been reported (11)(12)(13)(14)(15), suggesting that the dietary n-6/ n-3 ratio affects the life span of rats. However, the saturated : monounsaturated : polyunsaturated fatty acid ratio (S : M : P ratio) of test fats used in these experiments was not regulated, so it is not clear whether the influence on lifespan of the lipid type was caused by the n-6/ n-3 ratio.…”