Low Fatty Acid Unsaturation: A Mechanism for Lowered Lipoperoxidative Modification of Tissue Proteins in Mammalian Species With Long Life Spans

Pamplona, Reinald; Portero‐Otín, Manuel; Riba, D.; Requena, Jesús R.; Thorpe, Suzanne R.; López-Torres, Mónica; Barja, Gustavo

doi:10.1093/gerona/55.6.b286

Cited by 84 publications

(46 citation statements)

References 34 publications

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“…Thus the novel and unexpected finding that the composition of membrane bilayers varies systematically in mammals provided a link between metabolic rate and maximum life span of mammalian species. In agreement with this, it was demonstrated that in long-lived mammals, the low degree of membrane fatty acid unsaturation was accompanied by a low sensitivity to in vivo and in vitro lipid peroxidation (269,272,(275)(276)(277) and a low steady-state level of lipoxidation-derived adducts in both tissue and mitochondrial proteins of skeletal muscle, heart, liver, and brain (267,268,274,277,292,307). These findings were consistent with the negative correlation between MLSP and the sensitivity to lipid autoxidation of mammalian kidney and brain homogenates that had been described some years earlier (72).…”

Section: Membrane Composition Lipid Peroxidation Body Size and supporting

confidence: 66%

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

Hulbert¹,

Pamplona²,

Buffenstein

et al. 2007

Physiological Reviews

754

725

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Maximum life span differences among animal species exceed life span variation achieved by experimental manipulation by orders of magnitude. The differences in the characteristic maximum life span of species was initially proposed to be due to variation in mass-specific rate of metabolism. This is called the rate-of-living theory of aging and lies at the base of the oxidative-stress theory of aging, currently the most generally accepted explanation of aging. However, the rate-of-living theory of aging while helpful is not completely adequate in explaining the maximum life span. Recently, it has been discovered that the fatty acid composition of cell membranes varies systematically between species, and this underlies the variation in their metabolic rate. When combined with the fact that 1) the products of lipid peroxidation are powerful reactive molecular species, and 2) that fatty acids differ dramatically in their susceptibility to peroxidation, membrane fatty acid composition provides a mechanistic explanation of the variation in maximum life span among animal species. When the connection between metabolic rate and life span was first proposed a century ago, it was not known that membrane composition varies between species. Many of the exceptions to the rate-of-living theory appear explicable when the particular membrane fatty acid composition is considered for each case. Here we review the links between metabolic rate and maximum life span of mammals and birds as well as the linking role of membrane fatty acid composition in determining the maximum life span. The more limited information for ectothermic animals and treatments that extend life span (e.g., caloric restriction) are also reviewed.

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Section: Membrane Composition Lipid Peroxidation Body Size and supporting

confidence: 66%

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

Hulbert¹,

Pamplona²,

Buffenstein

et al. 2007

Physiological Reviews

754

725

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“…In this case, lower levels were observed in the brain of both parakeets and canaries compared to mice. Similarly, in every previous study performed to date, MDAL protein levels were always relatively lower in long-lived species, regardless of whether they were birds or mammals (Pamplona et al 1999(Pamplona et al , 2000Portero-Otin et al 2004;Ruiz et al 2005). MDAL is formed by covalent attachment of aldehydic functions of malondialdehyde (an important lipid peroxidation product) to lysine protein residues.…”

Section: Discussionmentioning

confidence: 74%

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

Pamplona

Portero‐Otín

Sanz

et al. 2005

AGE

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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.

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“…Although we have not measured ROS, it may be appropriate to mention that in vitro stimulation by iron and H 2 O 2 in the young and old animals result in an age-related decrease in the magnitude of response, which are correlated to alterations in the fatty acid composition during aging. An increase in MDA synthesis following iron and peroxide stimulation has been reported in aged mice [13,28]. Adult mice have better capacity to buffer exogenous stimuli and in contrast to aged mice, which are no longer able to counteract the enhanced production of MDA.…”

Section: Discussionmentioning

confidence: 99%

Regional responses in antioxidant system to exercise training and dietary Vitamin E in aging rat brain

Devi

Kiran

2004

Neurobiology of Aging

130

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We have evaluated the effect of exercise, Vitamin E and a combination of both on the antioxidant enzymes (AOEs)-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) along with the products of lipid peroxidation (LP)-malondialdehyde (MDA) and lipofuscin-like auto fluorescent substances (LF-like AFS) in discrete brain regions of rats of 4 (young adults), 8 (old adults), 12 (middle-age) and 22 months (mos) old of age. Hippocampus (HC) showed greater increase in GSH-Px activity than cerebral cortex (CC) to exercise and Vitamin E and was irrespective of the age. A combination of both was effective in the CC of all age groups but not in the supplemented sedentary of 12-and 22-mo-olds. CAT activity increased significantly in the HC of supplemented and trained rats but not in the combination group of any age. SOD increased in both the regions of supplemented trainees. However, old were more benefited in terms of maximal elevation in the HC. Vitamin E reduced MDA content in both regions of adult. LF-like AFS decreased significantly in supplemented sedentary and trainees of all ages. Our results demonstrate that an age-related deficit in AOEs in the CC and HC can be overcome through Vitamin E plus exercise, and further suggests the rationale for looking at these markers of oxidative stress in several age-related neuronal diseases.

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Low Fatty Acid Unsaturation: A Mechanism for Lowered Lipoperoxidative Modification of Tissue Proteins in Mammalian Species With Long Life Spans

Cited by 84 publications

References 34 publications

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

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

Regional responses in antioxidant system to exercise training and dietary Vitamin E in aging rat brain

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