Membrane lipids, damage & integrity 4 longevity

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Membrane lipid structure may matter to prevent their being damaged during aging. The below paper is pdf-availed. The CR, methionine-restriction and protein-restriction effects on membrane lipids in Table 3 interested me.

Pamplona R.Membrane phospholipids, lipoxidative damage and molecular integrity: A causal role in aging and longevity.Biochim Biophys Acta. 2008 Aug 5. [Epub ahead of print]PMID: 18721793

Abstract

Nonenzymatic molecular modifications induced by reactive carbonyl species (RCS) generated by peroxidation of membrane phospholipids acyl chains play a causal role in the aging process. Most of the biological effects of RCS, mainly alpha,â-unsaturated aldehydes, di-aldehydes, and keto-aldehydes, are due to their capacity to react with cellular constituents, forming advanced lipoxidation end-products (ALEs). Compared to reactive oxygen and nitrogen species, lipid-derived RCS are stable and can diffuse within or even escape from the cell and attack targets far from the site of formation. Therefore, these soluble reactive intermediates, precursors of ALEs, are not only cytotoxic per se, but they also behave as mediators and propagators of oxidative stress and cellular and tissue damage. The consequent loss-of-function and structural integrity of modified biomolecules can have a wide range of downstream functional consequences and may be the cause of

subsequent cellular dysfunctions and tissue damage. The causal role of ALEs in aging and longevity is inferred from the findings that follow: a) its accumulation with aging in several tissues and species; physiological interventions (dietary restriction) that increase longevity, decrease ALEs content; c) the longer the longevity of a species, the lower is the lipoxidation-derived molecular damage; and finally d) exacerbated levels of ALEs are associated with pathological states.

....

.... At the present time, several evidences seem to suggest that CR might delay aging and extend longevity through mechanisms that involve changes in the lipoxidative status.

Caloric, as well as protein and methionine restriction - nutritional interventions that increase longevity - attenuates age-related changes in the degree of membrane unsaturation and the level of lipoxidation-derived protein damage in a variety of tissues and animal species [96] and [129] (Table 3). Thus, a decrease in lipid peroxidation and lipoxidation-derived protein damage has been reported in CR flies (Drosophila; Pamplona et al., unpublished results), and tissues (liver and heart) from rats and mice [75], [76], [80], [96], [130], [131], [132], [133], [134], [135] and [136]. CR has also been shown to reduce levels of lipofuscin in tissues of rodents and C. elegans [23], [32], [84], [87], [137] and [138], as well as to decrease oxidative damage to mitochondrial DNA as measured by the levels of oxo8dG (reviewed in [3]). No data are available for DNA damaged by carbonyl compounds. The magnitude of the change is lower for membrane unsaturation

(between 2.5 and 10%) than that for the lipoxidation-derived molecular damage (between 20 and 40%) likely due to the added effect of the lower mitochondrial free radical generation also induced by these nutritional interventions. In addition to the moderate but significant effect on membrane unsaturation, these nutritional interventions show an effect that is directly related to the percent of the dietary restriction applied, being both protein and methionine restriction even more intense and effective that caloric restriction. The effects of CR on membrane unsaturation could be divided in three stages depending of CR duration in rats. During short-term CR periods, decreases in the rate of mitochondrial ROS production and lipoxidation-derived protein damage are observed in some tissues together with minor changes in membrane fatty acid composition. If CR is applied for several weeks-months, changes in particular fatty acids with moderate or no changes

in double bond content occur, although the magnitude of the changes depends on the organ and the intensity of the restriction. Finally, in long-term CR, the beneficial effects on ROS production, DBI-fatty acid composition, and lipoxidation-derived protein damage are evident. In fact, CR diminishes the slope of the relationship between age and age-related lipid peroxidation. Thus, the CR manipulation seems to trigger an adaptive response protecting the most basic requirements of membrane integrity.

Table 3. Effect of caloric- protein- and methionine restriction on membrane unsaturation and advanced lipoxidation end-products (ALEs) of different rat tissues.===========================================================Specie Tissue DR type (%) DR duration Effect on membrane unsaturation (PI) ALEs References ===========================================================Rat Liver mitochondria 8.5% CR 7 weeks Decreased Decreased [133] Rat Liver mitochondria 25% CR 7 weeks Decreased Decreased [133] Rat Heart mitochondria 40% CR 4 months Decreased Decreased [130] Rat Heart mitochondria 40% CR 1 year Decreased Decreased [80] Rat Liver mitochondria 40% CR 4-24 months Decreased Decreased [75] Rat Liver 40% CR 6 weeks Decreased Decreased [136] Rat Liver 40% PR 7 weeks Decreased Decreased [132] Rat Liver mitochondria 40% MetR 7 weeks Decreased Decreased [135] Rat Liver mitochondria 80% MetR 7 weeks Decreased

Decreased [131] and [135] Rat Heart mitochondria 80% MetR 7 weeks Decreased Decreased [131] Rat Brain 80% MetR 7 weeks Decreased Decreased [134]

Table 4. Comparative studies of membrane unsaturation in animal species with different maximum longevities.===========================================================Species compared Maximum longevity (years) Organ Correlation with maximum longevity References ===========================================================Rat-pigeon-human 4-120 mtLiver Negative [139] Rat vs pigeon 4, 35 mtLiver Negative [140] Rat vs pigeon 4, 35 mtHeart and microsomes Negative [140] 8 mammals 3.5-46 mtLiver Negative [141] Rat vs pigeon 4, 35 mtHeart Negative [142] 8 mammals 3.5-46 Heart Negative [143] Mouse vs canary 3.5, 24 Heart Negative [144] Mouse vs parakeet 3.5, 21 Heart Negative [144] 7 mammals 3.5-46 Liver Negative [145] 8 mammals 3.5, 46 mtLiver Negative [11] 11 mammals + 9 birds 3.5-120 Skeletal muscle Negative [146] and [147] 9 mammals + 8 birds 3.5-120 mtLiver Negative [148] and [149] Rat

vs pigeon 4, 35 Skeletal muscle Negative [150] Mouse, parakeet, canary 3.5, 21, 24 Brain Negative [151] 8 mammals 3.5-46 Heart Negative [152] SAM-R/1 vs SAM-P/1 mice 1.8, 1.2 Liver Negative [69] Strains of mice (Idaho, Majuro and WT) 3.97, 3.58, 3.35 Skeletal muscle and liver Negative [153] Mice vs naked mole-rats 3-4, 28 mtSkeletal muscle and mtLiver Negative [154] Queen honey bees vs workers 2-5, 75-135 days Head, thorax, abdomen Negative [155]

-- Aalt Pater

[Guest guest]

good site and article on lipoxidative damage. http://topics.scirus.com/LIPID_PEROXIDATION.html AnnAl Pater <old542000@...> wrote: Membrane lipid structure may matter to prevent their being damaged during aging. The below paper is pdf-availed. The CR, methionine-restriction and protein-restriction

effects on membrane lipids in Table 3 interested me. Pamplona R.Membrane phospholipids, lipoxidative damage and molecular integrity: A causal role in aging and longevity.Biochim Biophys Acta. 2008 Aug 5. [Epub ahead of print]PMID: 18721793 Abstract Nonenzymatic molecular modifications induced by reactive carbonyl species (RCS) generated by peroxidation of membrane phospholipids acyl chains play a causal role in the aging process. Most of the biological effects of RCS, mainly alpha,â-unsaturated aldehydes, di-aldehydes, and keto-aldehydes, are due to their capacity to react with cellular constituents, forming advanced lipoxidation end-products (ALEs). Compared to reactive oxygen and nitrogen species, lipid-derived RCS are stable and can diffuse within or even escape from the cell and attack targets far from the site of formation. Therefore, these soluble reactive intermediates,

precursors of ALEs, are not only cytotoxic per se, but they also behave as mediators and propagators of oxidative stress and cellular and tissue damage. The consequent loss-of-function and structural integrity of modified biomolecules can have a wide range of downstream functional consequences and may be the cause of subsequent cellular dysfunctions and tissue damage. The causal role of ALEs in aging and longevity is inferred from the findings that follow: a) its accumulation with aging in several tissues and species; physiological interventions (dietary restriction) that increase longevity, decrease ALEs content; c) the longer the longevity of a species, the lower is the lipoxidation-derived molecular damage; and finally d) exacerbated levels of ALEs are associated with pathological states. ... ... At the present time, several evidences seem to suggest that CR might delay aging and extend longevity

through mechanisms that involve changes in the lipoxidative status. Caloric, as well as protein and methionine restriction - nutritional interventions that increase longevity - attenuates age-related changes in the degree of membrane unsaturation and the level of lipoxidation-derived protein damage in a variety of tissues and animal species [96] and [129] (Table 3). Thus, a decrease in lipid peroxidation and lipoxidation-derived protein damage has been reported in CR flies (Drosophila; Pamplona et al., unpublished results), and tissues (liver and heart) from rats and mice [75], [76], [80], [96], [130], [131], [132], [133], [134], [135] and [136]. CR has also been shown to reduce levels of lipofuscin in tissues of rodents and C. elegans [23], [32], [84], [87], [137] and [138], as well as to decrease oxidative damage to mitochondrial DNA as measured by the levels of oxo8dG (reviewed in [3]). No data are available for DNA damaged by

carbonyl compounds. The magnitude of the change is lower for membrane unsaturation (between 2.5 and 10%) than that for the lipoxidation-derived molecular damage (between 20 and 40%) likely due to the added effect of the lower mitochondrial free radical generation also induced by these nutritional interventions. In addition to the moderate but significant effect on membrane unsaturation, these nutritional interventions show an effect that is directly related to the percent of the dietary restriction applied, being both protein and methionine restriction even more intense and effective that caloric restriction. The effects of CR on membrane unsaturation could be divided in three stages depending of CR duration in rats. During short-term CR periods, decreases in the rate of mitochondrial ROS production and lipoxidation-derived protein damage are observed in some tissues together with minor changes in membrane fatty acid composition. If CR is applied for several

weeks-months, changes in particular fatty acids with moderate or no changes in double bond content occur, although the magnitude of the changes depends on the organ and the intensity of the restriction. Finally, in long-term CR, the beneficial effects on ROS production, DBI-fatty acid composition, and lipoxidation-derived protein damage are evident. In fact, CR diminishes the slope of the relationship between age and age-related lipid peroxidation. Thus, the CR manipulation seems to trigger an adaptive response protecting the most basic requirements of membrane integrity. Table 3. Effect of caloric- protein- and methionine restriction on membrane unsaturation and advanced lipoxidation end-products (ALEs) of different rat tissues.===========================================================Specie Tissue DR type (%) DR duration Effect on membrane unsaturation (PI) ALEs References

===========================================================Rat Liver mitochondria 8.5% CR 7 weeks Decreased Decreased [133] Rat Liver mitochondria 25% CR 7 weeks Decreased Decreased [133] Rat Heart mitochondria 40% CR 4 months Decreased Decreased [130] Rat Heart mitochondria 40% CR 1 year Decreased Decreased [80] Rat Liver mitochondria 40% CR 4-24 months Decreased Decreased [75] Rat Liver 40% CR 6 weeks Decreased Decreased [136] Rat Liver 40% PR 7 weeks Decreased Decreased [132] Rat Liver mitochondria 40% MetR 7 weeks Decreased Decreased [135] Rat Liver mitochondria 80% MetR 7 weeks Decreased Decreased [131] and [135] Rat Heart mitochondria 80% MetR 7 weeks Decreased Decreased [131] Rat Brain 80% MetR 7 weeks Decreased Decreased [134] Table 4. Comparative studies of membrane unsaturation in animal species with different maximum

longevities.===========================================================Species compared Maximum longevity (years) Organ Correlation with maximum longevity References ===========================================================Rat-pigeon-human 4-120 mtLiver Negative [139] Rat vs pigeon 4, 35 mtLiver Negative [140] Rat vs pigeon 4, 35 mtHeart and microsomes Negative [140] 8 mammals 3.5-46 mtLiver Negative [141] Rat vs pigeon 4, 35 mtHeart Negative [142] 8 mammals 3.5-46 Heart Negative [143] Mouse vs canary 3.5, 24 Heart Negative [144] Mouse vs parakeet 3.5, 21 Heart Negative [144] 7 mammals 3.5-46 Liver Negative [145] 8 mammals 3.5, 46 mtLiver Negative [11] 11 mammals + 9 birds 3.5-120 Skeletal muscle Negative [146] and [147] 9 mammals + 8 birds 3.5-120 mtLiver Negative [148] and [149] Rat vs pigeon 4, 35 Skeletal muscle Negative [150] Mouse,

parakeet, canary 3.5, 21, 24 Brain Negative [151] 8 mammals 3.5-46 Heart Negative [152] SAM-R/1 vs SAM-P/1 mice 1.8, 1.2 Liver Negative [69] Strains of mice (Idaho, Majuro and WT) 3.97, 3.58, 3.35 Skeletal muscle and liver Negative [153] Mice vs naked mole-rats 3-4, 28 mtSkeletal muscle and mtLiver Negative [154] Queen honey bees vs workers 2-5, 75-135 days Head, thorax, abdomen Negative [155] -- Aalt PaterAnn