N−3 polyunsaturated fatty acids impair lifespan but have no role for metabolism

Abstract

SummaryAlthough generally considered as beneficial components of dietary fats, polyunsaturated fatty acids (PUFA) have been suspected to compromise maximum lifespan (MLSP) in mammals. Specifically, high amounts of phospholipid PUFAs are thought to impair lifespan due to an increase in the susceptibility of membranes to lipid peroxidation and its damaging effect on cellular molecules. Also, there is evidence from in vitro studies suggesting that highly unsaturated PUFAs elevate basal metabolic rate (BMR). Previous comparative studies in this context were based on small sample sizes, however, and, except for one study, failed to address possible confounding influences of body weight and taxonomic relations between species. Therefore, we determined phospholipid membrane composition in skeletal muscle from 42 mammalian species to test for a relation with published data on MLSP, and with literature data on BMR (30 species). Using statistical models that adjust for the effects of body weight and phylogeny, we found that among mammals, MLSP indeed decreases as the ratio of n− − − − 3 to n− − − − 6 PUFAs increases. In contrast to previous studies, we found, however, no relation between MLSP and either membrane unsaturation (i.e. PUFA content or number of double bonds) or to the very longchain, highly unsaturated docosahexaenoic acid (DHA). Similarly, our data set gave no evidence for any notable relation between muscle phospholipid fatty acid composition and BMR, or MLSP and BMR in mammals. These results contradict the 'membrane pacemaker theory of aging', that is, the concept of a direct link between high amounts of membrane PUFAs, elevated BMR, and thus, impaired longevity.

Setting the pace of life: membrane composition of flight muscle varies with metabolic rate of hovering orchid bees

“…Our results illustrate a recurring conundrum in similar studies, such as in experimental evolution studies [28] or studies controlling for body mass and phylogeny [26] that seldom find strong support for the pacemaker hypothesis. Nonetheless, we did find a direct relationship between FlightMR and the abundance of the saturated FA 16 : 0, after controlling for body mass and phylogeny (figure 5).…”

Rediscovering and Reviving Old Observations and Explanations of Metabolic Scaling in Living Systems

“…Recent investigators have implicated membrane composition and function [89,167,179,234], mitochondrial activity and number [97,179,[235][236][237], intracellular transport costs [130], DNA content [182,190], and other biochemical factors [238], as importantly involved in the intrinsic cellular control of metabolic scaling. Evidence for and against various specific aspects of this approach can be found in [19,20,89,[91][92][93][94]130,167,169,[235][236][237][238][239][240][241][242][243]. A major limitation of the cell-based RD approach is that it cannot explain by itself why the hypometric scaling of cellular metabolic rate is lost in cells cultured in vivo (reviewed in [20,97]).…”

Explaining longevity of different animals: is membrane fatty acid composition the missing link?

“…3 Relationship between maximum life span of mammals and birds and peroxidation index of skeletal muscle phospholipids (a) and liver mitochondrial phospholipids (b). Skeletal muscle data combined from Valencak and Ruf (2007) and those cited in Hulbert (2005); liver mitochondrial data combined from Pamplona et al (1998) and those cited in Hulbert (2005).…”