Regulation of Membrane Unsaturation as Antioxidant Adaptive Mechanism in Long-lived Animal Species

Abstract

Oxidative stress resulting from biomolecular oxidative damage due to the imbalance between reactive species production and antioxidant response has become an universal constraint of life-history evolution in animals and a modulator of phenotypic development and trade-offs. Redox balance is an important selective pressure faced by most organisms, and a myriad of mechanisms have evolved to regulate and adjust this balance. This diversity of mechanisms means that organisms have a great deal of flexibility in how they deal with reactive species challenges across time, conditions, and tissue types, as well as that different organisms may evolve different strategies for dealing with similar challenges. In the following paragraphs, we review the adaption of biological membranes as structural antioxidant defense against reactive species evolved by animals. In particular, it is our goal to describe the physiological mechanisms underlying the structural adaption of cellular membranes to oxidative stress, to explain the meaning of this adaptive mechanism, and to review the state of the art about the link between membrane composition and longevity of animal species.

Exceptionally old mice are highly resistant to lipoxidation-derived molecular damage

“…Available evidence supports the hypothesis that membrane fatty acid composition is regulated in a longevity-related species-specific way (Naudi et al 2011). As a whole, the membrane acyl composition of the studied groups (adult, old and exceptionally old) verifies that their biological membranes maintain, for both brain and spleen, a similar fatty acid average chain length (18 carbon atoms), as well as ratio saturated versus unsaturated fatty acids (ratiõ 40:60) ( Table 1).…”

“…The maintenance of the double bond index and peroxidizability index at levels of the adult group in exceptionally old animals can be appointed to the preservation of the content of specific fatty acids, particularly 20:4 and 22:6 (Table 2). Mechanisms responsible for the longevity-related differences in fatty acid profile can be related, in principle, to the fatty acid desaturation-elongation pathway (Naudi et al 2011). For this reason, different desaturase and elongase activities, as well as the peroxisomal β-oxidation activity, were estimated from specific product/substrate ratios.…”

“…Of special interest is the Hulbert et al 2007;Pamplona 2008;Naudi et al 2011) based on studies showing decreases in membrane fluidity with age and increases in membrane lipid peroxidation during aging in an organdependent way mainly due to decreases in monoand di-unsaturated fatty acids and to increases in highly unsaturated fatty acids like 20:4 and 22:6. In addition to these findings, the animal model senescent accelerated prone mouse (SAM-P) has higher levels of the highly unsaturated arachidonic (20:4) and docosahexaenoic (22:6) acids and lower levels of linoleic acid than SAM-resistant controls (Park et al 1996;Matsugo et al 2000).…”

The Mitochondrial Free Radical Theory of Aging

“…5 A total of 23 studies extended the first seminal observation to many different mammals, various bird species, and some invertebrates, without finding a single exception. 6 Since the low degree of unsaturation occurs both in mitochondrial and in total cellular membranes in long-lived animals, it can diminish lipoxidation-derived damage in various cellular compartments including the mitochondrial one where there is strong abundance of membranes.…”

“…Presently, only two known factors correlate in the right sense with animal longevity in vertebrates including mammals and birds: (a) the rate of mitochondrial reactive oxygen species production (mtROSp) [1][2][3][4] and (b) the degree of fatty acid unsaturation of tissue cellular membranes including the mitochondrial ones. 5,6 The longer the longevity of a species, the smaller these two parameters are. The decrease in mtROSp in long-lived animal species lowers their generation of endogenous (free radical) damage at mitochondria.…”