Protein and lipid oxidative damage and complex I content are lower in the brain of budgerigar and canaries than in mice. Relation to aging rate

Abstract

What are the mechanisms determining the rate of animal aging? Of the two major classes of endothermic animals, bird species are strikingly long-lived compared to mammals of similar body size and metabolic rate. Thus, they are ideal models to identify longevity-related characteristics not linked to body size or low metabolic rates. Since oxidative stress seems to be related to the basic aging process, we measured specific markers of different kinds of oxidative damage to proteins, like glutamic and aminoadipic semialdehydes (GSA and AASA, specific protein carbonyls), N(-(carboxyethyl)lysine (CEL), N(-(carboxymethyl)lysine (CML), and N(-(malondialdehyde)lysine (MDAL), as well as mitochondrial Complex I content and amino acid and membrane fatty acyl composition, in the brain of short-lived mice (maximum life span [MLSP] 3.5 years) compared with those of long-lived budgerigar Fparakeets_ (MLSP, 21 years) and canaries (MLSP, 24 years). The brains of both bird species had significantly lower levels of compounds formed as a result of oxidative (GSA and AASA), glycoxidative (CEL and CML), and lipoxidative (CML and MDAL) protein modifications, as well as a lower levels of mitochondrial complex I protein. Although it is known that fatty acid unsaturation is lower in many tissues of long-lived compared to short-lived mammals, this is not true in the particular case of brain. In agreement with this, we also found that the brain tissue of bugerigars and canaries contains no fewer double bonds than that of mice. Amino acid composition analyses revealed that bird proteins have a significantly lower content of His, Leu and Phe, as well as, interestingly, of methionine, whereas Asp, Glu, Ala, Val, and Lys contents were higher than in the mammals. These results, together with those previously described in other tissues of pigeons (MLSP, 35 years) compared to rats (MLSP, 4 years), indicate that oxidative damage to proteins, lipids and mitochondrial DNA are lower in birds (very long-lived species) than in short-lived mammals of similar body size. The lower degree of oxidative modification of bird brain proteins was not due to decreases in the target amino acids (lysine for CEL, CML, MDAL, and AASA; and arg and pro for GSA), since these were present in bird brain proteins at higher or similar levels than in those of mice. These results are consistent with the possibility that decreases in oxidative protein modification are caused at least in part by the low rate of mitochondrial oxygen radical generation in these birds, as in all long-lived homeothermic vertebrates investigated so far.

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

“…Fatty acyl groups of total brain and spleen lipids were analysed as methyl esters derivatives by gas chromatography (GC) as previously described (Pamplona et al 2005a(Pamplona et al , 2005b. Total lipids were extracted with chloroform/methanol (2:1, v/v) in the presence of 0.01% butylated hydroxytoluene.…”

“…The following fatty acyl indexes (Pamplona et al 2005a(Pamplona et al , 2005bHulbert et al 2007) were also calculated: saturated fatty acids, unsaturated fatty acids, monounsaturated fatty acids, PUFA, PUFA from n-3 and n-6 series and average chain length0[(Σ%Total 14 ×14)+ (Σ% Total 16 ×16)+(Σ%Total 18 ×18)+(Σ%Total 20 ×20)+ (Σ% Total 22 ×22)+(Σ% Total 24 ×24)]/100. The density of double bonds in the membrane was calculated by the double bond index (DBI)0[(1×Σmol% monoenoic)+ (2×Σmol% dienoic)+(3×Σmol% trienoic)+(4×Σmol% tetraenoic) + (5 × Σmol% pentaenoic) + (6 × Σmol% hexaenoic)].…”

“…Five oxidative damage markers of protein oxidation (the specific protein carbonyls glutamic and aminoadipic semialdehydes, GSA and AASA), glycoxidation (carboxyethyl-lysine CEL) and lipoxidation (CML and MDAL) were measured by GC/mass spectrometry (MS) as previously described (Pamplona et al 2005a(Pamplona et al , 2005b. Samples (brain and spleen homogenates) containing 500 μg of protein were delipidated using chloroform/methanol (2:1, v/v), and proteins were precipitated by adding 10% trichloroacetic acid (final concentration) and subsequent centrifugation.…”

Exercise modulation of total antioxidant capacity (TAC): towards a molecular signature of healthy aging

“…In fact, oxidative/nitrosative stresses in aging depend on age, gender, smoking, alcohol drinking, body composition, genome, and other intrinsic and extrinsic factors (Lesgards et al 2002;Gutteridge and Halliwell 2010). However, since the 1950s a great number of studies have been reported increased oxidative/nitrosative stresses and decreased cell antioxidant defenses in aging animals and humans (Ferrari 2004;Barja 2005;Pamplona et al 2005; da Silva and Ferrari 2011).…”

Comparative and alternative approaches and novel animal models for aging research

“…For this reason, proponents of rigorous evolutionary comparative methods strongly discourage tests of hypotheses employing comparisons of only two species or taxa along a given phenotypic continuum of interest (Rose 1991;Garland and Adolph 1994;Austad and Holmes 1999). While two-species comparisons can be heuristic for generating hypotheses about possible aging mechanisms (e.g., Ku and Sohal 1993;Barja 1998;Pamplona et al 2005), these comparisons have limited value for making strong inferences about physiological adaptation vs phylogenetic effects.…”