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Plasma long-chain free fatty acids predict mammalian longevity.

Jové M, Naudí A, Aledo JC, Cabré R, Ayala V, Portero-Otin M, Barja G, Pamplona R - Sci Rep (2013)

Bottom Line: Membrane lipid composition is an important correlate of the rate of aging of animals and, therefore, the determination of their longevity.The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence.These results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida (IRBLleida), E-25198 Lleida, Spain.

ABSTRACT
Membrane lipid composition is an important correlate of the rate of aging of animals and, therefore, the determination of their longevity. In the present work, the use of high-throughput technologies allowed us to determine the plasma lipidomic profile of 11 mammalian species ranging in maximum longevity from 3.5 to 120 years. The non-targeted approach revealed a specie-specific lipidomic profile that accurately predicts the animal longevity. The regression analysis between lipid species and longevity demonstrated that the longer the longevity of a species, the lower is its plasma long-chain free fatty acid (LC-FFA) concentrations, peroxidizability index, and lipid peroxidation-derived products content. The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence. These results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity.

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Relationship between maximum longevity (MLSP) and double bond index (DBI) (A), peroxidizability index (PI) (B) and specific lipid peroxidation-derived products of plasma in mammalian species (C–D).Curve estimation (inverse mode) equation: Y = b0 + (b1/MLSP): Doble bond index: b0 = 62.235, b1 = 93.398; Peroxidizability index: b0 = 32.687, b1 = 95.311; hydroxyoctadecadienoic acid (HODE): b0 = 3.78, b1 = 6.338; 10-hydroxy-docosahexaenoic acid (10-hydroxy-DHA): b0 = −0.326, b1 = 7.827. N × group: 9–15 animals. Values are means ± SEM.
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f3: Relationship between maximum longevity (MLSP) and double bond index (DBI) (A), peroxidizability index (PI) (B) and specific lipid peroxidation-derived products of plasma in mammalian species (C–D).Curve estimation (inverse mode) equation: Y = b0 + (b1/MLSP): Doble bond index: b0 = 62.235, b1 = 93.398; Peroxidizability index: b0 = 32.687, b1 = 95.311; hydroxyoctadecadienoic acid (HODE): b0 = 3.78, b1 = 6.338; 10-hydroxy-docosahexaenoic acid (10-hydroxy-DHA): b0 = −0.326, b1 = 7.827. N × group: 9–15 animals. Values are means ± SEM.

Mentions: Regression curve analysis shows that there is a negative correlation between animal longevity and plasma FFAs. Indeed the longer the longevity of a species, the lower is its plasma LC-FFA concentration. The plasma LC-FFA composition and derived parameters in the 11 animal species studied in this investigation is shown in Supplementary Table S2. This was due to the negative correlation with MLSP for all the LC-FFAs [myristic acid (C14:0): R2 = 0.644, p < 0.003; palmitic acid (C16:0): R2 = 0.706, p < 0.001; stearic acid (C18:0): R2 = 0.687, p < 0.002; oleic acid (C18:1n − 9): R2 = 0.621, p < 0.004; linoleic acid (C18:2n − 6): R2 = 0.769, p < 0.0001; arachidonic acid (C20:4n − 6): R2 = 0.636, p < 0.003; and docosahexaenoic acid (DHA) (C22:6n − 3): R2 = 0.570, p < 0.007] (Fig. 2) being also significant the correlation between total LC-FFAs and the MLSP (R2 = 0.73, p < 0.001). In contrast, no correlations were observed for medium-chain FFAs (capric acid, C10:0; and lauric acid, C12:0) nor for the average chain length (ACL) (data not shown). The density of double bonds in FFAs (double bond index (DBI)) and susceptibility to peroxidation (peroxidizability index, PI, which takes into account that the sensitivity to peroxidation increases as an exponential function of the number of double bonds per fatty acid) (Fig. 3) showed significant negative correlations with MLSP (R2 = 0.706, p < 0.001; and R2 = 0.691, p < 0.002, respectively). In addition, due to the importance of oxidative stress in animal longevity2 we focused in several lipid peroxidation products, by using a targeted lipidomic approach. Among them, we specifically detected and quantified the hydroperoxides 9- and 13-hydroxy-octadecadienoic acid (HODE) and the 10-hydroxy-DHA. In agreement with the lower DBI and PI of long-lived animals, this was also reflected in the endogenous content of lipid peroxidation products from very LC-FFAs, since the in vivo lipid peroxidation of plasma samples was also negatively correlated with the MLSP of the animal species (HODE: R2 = 0.529, p < 0.011; 10-hydroxy-DHA: R2 = 0.753, p < 0.001) (Fig. 3).


Plasma long-chain free fatty acids predict mammalian longevity.

Jové M, Naudí A, Aledo JC, Cabré R, Ayala V, Portero-Otin M, Barja G, Pamplona R - Sci Rep (2013)

Relationship between maximum longevity (MLSP) and double bond index (DBI) (A), peroxidizability index (PI) (B) and specific lipid peroxidation-derived products of plasma in mammalian species (C–D).Curve estimation (inverse mode) equation: Y = b0 + (b1/MLSP): Doble bond index: b0 = 62.235, b1 = 93.398; Peroxidizability index: b0 = 32.687, b1 = 95.311; hydroxyoctadecadienoic acid (HODE): b0 = 3.78, b1 = 6.338; 10-hydroxy-docosahexaenoic acid (10-hydroxy-DHA): b0 = −0.326, b1 = 7.827. N × group: 9–15 animals. Values are means ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842621&req=5

f3: Relationship between maximum longevity (MLSP) and double bond index (DBI) (A), peroxidizability index (PI) (B) and specific lipid peroxidation-derived products of plasma in mammalian species (C–D).Curve estimation (inverse mode) equation: Y = b0 + (b1/MLSP): Doble bond index: b0 = 62.235, b1 = 93.398; Peroxidizability index: b0 = 32.687, b1 = 95.311; hydroxyoctadecadienoic acid (HODE): b0 = 3.78, b1 = 6.338; 10-hydroxy-docosahexaenoic acid (10-hydroxy-DHA): b0 = −0.326, b1 = 7.827. N × group: 9–15 animals. Values are means ± SEM.
Mentions: Regression curve analysis shows that there is a negative correlation between animal longevity and plasma FFAs. Indeed the longer the longevity of a species, the lower is its plasma LC-FFA concentration. The plasma LC-FFA composition and derived parameters in the 11 animal species studied in this investigation is shown in Supplementary Table S2. This was due to the negative correlation with MLSP for all the LC-FFAs [myristic acid (C14:0): R2 = 0.644, p < 0.003; palmitic acid (C16:0): R2 = 0.706, p < 0.001; stearic acid (C18:0): R2 = 0.687, p < 0.002; oleic acid (C18:1n − 9): R2 = 0.621, p < 0.004; linoleic acid (C18:2n − 6): R2 = 0.769, p < 0.0001; arachidonic acid (C20:4n − 6): R2 = 0.636, p < 0.003; and docosahexaenoic acid (DHA) (C22:6n − 3): R2 = 0.570, p < 0.007] (Fig. 2) being also significant the correlation between total LC-FFAs and the MLSP (R2 = 0.73, p < 0.001). In contrast, no correlations were observed for medium-chain FFAs (capric acid, C10:0; and lauric acid, C12:0) nor for the average chain length (ACL) (data not shown). The density of double bonds in FFAs (double bond index (DBI)) and susceptibility to peroxidation (peroxidizability index, PI, which takes into account that the sensitivity to peroxidation increases as an exponential function of the number of double bonds per fatty acid) (Fig. 3) showed significant negative correlations with MLSP (R2 = 0.706, p < 0.001; and R2 = 0.691, p < 0.002, respectively). In addition, due to the importance of oxidative stress in animal longevity2 we focused in several lipid peroxidation products, by using a targeted lipidomic approach. Among them, we specifically detected and quantified the hydroperoxides 9- and 13-hydroxy-octadecadienoic acid (HODE) and the 10-hydroxy-DHA. In agreement with the lower DBI and PI of long-lived animals, this was also reflected in the endogenous content of lipid peroxidation products from very LC-FFAs, since the in vivo lipid peroxidation of plasma samples was also negatively correlated with the MLSP of the animal species (HODE: R2 = 0.529, p < 0.011; 10-hydroxy-DHA: R2 = 0.753, p < 0.001) (Fig. 3).

Bottom Line: Membrane lipid composition is an important correlate of the rate of aging of animals and, therefore, the determination of their longevity.The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence.These results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine, University of Lleida-Biomedical Research Institute of Lleida (IRBLleida), E-25198 Lleida, Spain.

ABSTRACT
Membrane lipid composition is an important correlate of the rate of aging of animals and, therefore, the determination of their longevity. In the present work, the use of high-throughput technologies allowed us to determine the plasma lipidomic profile of 11 mammalian species ranging in maximum longevity from 3.5 to 120 years. The non-targeted approach revealed a specie-specific lipidomic profile that accurately predicts the animal longevity. The regression analysis between lipid species and longevity demonstrated that the longer the longevity of a species, the lower is its plasma long-chain free fatty acid (LC-FFA) concentrations, peroxidizability index, and lipid peroxidation-derived products content. The inverse association between longevity and LC-FFA persisted after correction for body mass and phylogenetic interdependence. These results indicate that the lipidomic signature is an optimized feature associated with animal longevity, emerging LC-FFA as a potential biomarker of longevity.

Show MeSH
Related in: MedlinePlus