Abstract
Free radical damage is considered a determinant factor in the rate of aging. Unsaturated fatty acids are the tissue macromolecules that are most sensitive to oxidative damage. Therefore, the presence of low proportions of fatty acid unsaturation is exprected in the tissues of long-lived animals. Accordingly, the fatty acid compositions of the major liver mitochondrial phospholipid classes from eight mammals, ranging in maximum life span potential (MLSP) from 3.5 to 46 yr, show that the total number of double bonds is inversely correlated with MLSP in both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) (r=0.757, P<0.03, and r=0.862, P<0.006, respectively), but not in cardiolipin (P=0.323). This is due not to a low content of unsaturated fatty acids in long-lived animals, but mainly to a redistribution between kinds of fatty acids on PtdCho and PtdEtn, shifting from arachidonic (r=0.911, P<0.002, and r=0.681, P=0.05, respectively), docosahexaenoic (r=0.931 and r=0.965, P<0.0001, respectively) and palmitic (r=0.944 and r=0.974, P<0.0001, respectively) acids to linoleic acid (r=0.942, P<0.0001, for PtdCho; and r=0.957, P<0.0001, for PtdEtn). For cardiolipin, only arachidonic acid showed a significantly inverse correlation with MLSP (r=0.904, P<0.002). This pattern strongly suggests the presence of a species-specific desaturation pathway and deacylation-reacylation cycle in determining the mitochondrial membrane composition, maintaining a low degree of fatty acid unsaturation in long-lived animals.
Similar content being viewed by others
Abbreviations
- AA:
-
arachidonic acid
- ACL:
-
average chain length
- DBI:
-
double bond index
- DHA:
-
docosahexaenoic acid
- GC-MS:
-
gas chromatography-mass spectrometry
- LA:
-
linoleic acid
- MLSP:
-
maximum life span potential
- MSE:
-
buffer, mannitol, sucrose, and EGTA at pH 7.4
- MUFA:
-
monounsaturated fatty acids
- PtdCho:
-
phosphatidylcholine
- PtdEtn:
-
phosphatidylethanolamine
- PUFA:
-
polyunsaturated fatty acid
- SFA:
-
saturated fatty acids
- TLC:
-
thin-layer chromatography
- UFA:
-
unsaturated fatty acids
References
Cadenas, E., and Packer, L. (1999) Understanding the Process of Aging. The Roles of Mitochondria, Free Radicals, and Antioxidants, pp. 1–360, Marcel Dekker, New York.
Sohal, R.S., Svensson, I., and Brunk, U.T. (1990) Hydrogen Per oxide Production by Liver Mitochondria in Different Species, Mech. Ageing Dev. 53, 209–215.
Barja, G. (1999) Mitochondrial Oxygen Radical Generation and Leak: Sites of Production in States 4 and 3, Organ Specificity, and Relation to Aging and Longevity, J. Bioenerg. Biomembr. 31, 347–366.
Adelman, R., Saul, R.L., and Ames, B.N. (1988) Oxidative Damage to DNA: Relation to Species Metabolic Rate and Life Span, Proc. Natl. Acad. Sci. USA 85, 2706–2708.
Barja, G., and Herrero, A. (2000) Oxidative Damage to Mitochondrial DNA Is Inversely Related to Maximum Life Span in the Heart and Brain of Mammals, FASEB J. 14, 312–318.
Harman, D. (1994) Free Radical Theory of Aging. Increasing the Functional Life Span, Ann. NY Acad. Sci. 717, 1–15.
Yu, B.P., and Yang, R. (1996) Critical Evaluation of the Free Radical Theory of Aging. A Proposal for the Oxidative Stress Hypothesis, Ann. NY Acad. Sci. 786, 1–11.
Pamplona, R., Prat, J., Cadenas, S., Rojas, C., Perez-Campo, R., Lopez-Torres, M., and Barja, G. (1996) Low Fatty Acid Unsaturation Protects Against Lipid Peroxidation in Liver Mitochondria from Longevous Species: the Pigeon and Human Case, Mech. Ageing Dev. 86, 53–66.
Pamplona, R., Portero-Otín, M., Riba, D., Ruiz, C., Prat, J., Bellmunt, M.J., and Barja, G. (1998) Mitochondrial Membrane Peroxidizability Index Is Inversely Related to Maximum Life Span in Mammals, J. Lipid Res. 39, 1989–1994.
Pamplona, R., Portero-Otín, M., Requena, J.R., Torpe, S.R., Herrero, A., and Barja, G. (1999) A Low Degree of Fatty Acid Unsaturation Leads to Lower Lipid Peroxidation and Lipoxidation-Derived Protein Modification in Heart Mitochondria of the Longevous Pigeon Than in the Short-Lived Rat, Mech. Ageing Dev. 106, 283–296.
Pamplona, R., Portero-Otín, M., Ruiz, C., Gredilla, R., Herrero, A., and Barja, G. (2000) Double Bond Content of Phospholipids and Lipid Peroxidation Negatively Correlate with Maximum Longevity in the Heart of Mammals, Mech. Ageing Dev. 112, 169–183.
Pamplona, R., Portero-Otín, M., Riba, D., Requena, J.R., Thorpe, S.R., López-Torres, M., and Barja, G. (2000) Low Fatty Acid Unsaturation: a Mechanism for Lowered Lipoperoxidative Modification of Tissue Proteins in Mammalian Species with Long Life Span, J. Gerontol. A Biol. Sci. Med. Sci. 55A, B286-B291.
Cutler, R.G. (1985) Peroxide-Producing Potential of Tissues: Inverse Correlation with Longevity of Mammalian Species, Proc. Natl. Acad. Sci. USA 82, 4798–4802.
Daum, G. (1985) Lipids of Mitochondria, Biochim. Biophys. Acta 822, 1–42.
Dowhan, W. (1997) Molecular Basis for Membrane Phospholipid Diversity: Why Are There So Many Lipids? Annu. Rev. Biochem. 66, 199–232.
Altman, P.L., and Dittmer, D.S. (1972) Biology Data Book, Vol. 1, pp. 29–230, Federation of American Societies of Experimental Biology, Bethesda.
Graham, J.M. (1993) Biomembranes Protocols, in Methods in Molecular Biology 19 (Graham, J.M., and Higgins, J.A., eds.), p. 1, Humana Press, Totowa, NJ.
Folch, J., Lees, M., and Sloane-Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues, J. Biol. Chem. 226, 497–509.
Segura, R., Navarro, X., Prat, J., and Martin, S. (1985) A New System Allowing the Simultaneous Fractionation of the Different Non-ionic and Phospholipid Classes by Mono-dimensional Thin Layer Chromatography, XXI International Symposium on Advances in Chromatography, Oslo.
Gutierrez, A.M., Reboredo, G.R., Arcemis, C.J., and Catalá, A. (1997) Non-enzymatic Lipid Peroxidation of Microsomes and Mitochondria Isolated from Liver and Heart of Pigeon and Rat, Int. J. Biochem. Cell Biol. 32, 73–79.
Gudbjarnason, S. (1989) Dynamics of n-3 and n-6 Fatty Acids in Phospholipids of Heart Muscle, J. Intern. Med. 225, 117–128.
Couture, P., and Hulbert, A.J. (1995) Membrane Fatty Acid Composition of Tissues Is Related to Body Mass of Mammals, J. Membr. Biol. 148, 27–39.
Infante, J.P., and Huszagh, V.A. (1998) Analysis of the Putative Role of 24-Carbon Polyunsaturated Fatty Acids in the Biosynthesis of Docosapentaenoic (22∶5n-6) and Docosahexaenoic (22∶6n-3) Acids, FEBS Lett. 431, 1–6.
Hatch, G.M. (1998) Cardiolipin: Biosynthesis, Remodelling and Trafficking in the Heart and Mammalian Cells, Int. J. Mol. Med. 1, 33–41.
Cocco, T., Di Paola, M., Papa, S., and Lorusso, M. (1999) Arachidonic Acid Interaction with Mitochondrial Electron Transport Chain Promotes Reactive Oxygen Species Generation, Free Radicals Biol. Med. 27, 51–59.
Perez-Campo, R., Lopez-Torres, M., Cadenas, S., Rojas, C., and Barja, G. (1998) The Rate of Free Radical Production as a Determinant of the Rate of Aging: Evidence from the Comparative Approach, J. Comp. Physiol. B 168, 149–158.
Charnock, J.S., Abeywardena, M.Y., Poletti, V.M., and McLennan, P.L. (1992) Differences in Fatty Acid Composition of Various Tissues of the Marmoset Monkey (Callithrix jacchus) After Different Lipid-Supplemented Diets, Comp. Biochem. Physiol. 101A, 387–393.
Finch, C.E., and Tanzi, R.E. (1997) Genetics of Aging, Science 278, 407–411.
Solà, R., La Ville, A.E., Richard, J.L., Motta, C., Bargalló, M.T., Girona, J., Masana, L., and Jacotot, B. (1997) Dleic Acid Rich Diet Protects Against the Oxidative Modification of High Density Lipoprotein, Free Radicals Biol. Med. 22, 1037–1045.
Couture, P., and Hulbert, A.J. (1995) Relationship Between Body Mass, Tissue Metabolic Rate, and Sodium Pump Activity in Mammalian Liver and Kidney, Am. J. Physiol. 268, R645-R650.
Porter, R.K., and Brand, M. (1993) Body Mass Dependence of H+ Leak in Mitochondria and Its Relevance to Metabolic Rate, Nature 362, 628–629.
Forsmark-Andrée, P., Dallner, G., and Ernster, L. (1995) Endogenous Ubiquinol Prevents Protein Modification Accompanying Lipid Peroxidation in Beef Heart Submitochondrial Particles, Free Radicals Biol. Med. 19, 749–757.
Sato, A., Huang, M.Z., Watanabe, S., Okyama, H., Nakamoto, H., Radák, Z., and Goto, S. (1998) Protein Carbonyl Content Roughly Reflects the Unsaturation of Lipids in Muscle but not in Other Tissues of Stroke-prone Spontaneously Hypertensive Strain (SHRSP) Rats Fed Different Fats and Oils, Biol. Pharm. Bull. 21, 1271–1276.
Refsgaard, H.H.F., Tsai, L., and Stadtman, E.R. (2000) Modifications of Proteins by Polyunsaturated Fatty Acid Peroxidation Products, Proc. Natl. Acad. Sci. USA 97, 611–616.
Draper, H.H. (1995) Effects of Peroxidative Stress and Age on the Concentration of a Deoxyguanosine-Malondialdehyde Adduct in Rat DNA, Lipids 30, 959–961.
Laganiere, S., and Yu, B.P. (1987) Anti-lipoperoxidation Action of Food Restriction, Biochem. Biophys. Res. Commun. 145, 1185–1191.
Laganiere, S., and Yu, B.P. (1989) Effect of Chronic Food Restriction in Aging Rats. I. Liver Subcellular Membranes, Mech. Ageing Dev. 48, 221–230.
Laganiere, S., and Yu, B.P. (1993) Modulation of Membrane Phospholipid Fatty Acid Composition by Age and Food Restriction, Gerontology 39, 7–18.
Porta, E.A. (1988) Role of Oxidative Damage in the Aging Process, in Cellular Antioxidant Defense Mechanisms (Chow, C.K., ed.), Vol. 8, pp. 2–52, CRC Press, Boca Raton.
Yu, B.P., Laganiere, S., and Kim, J.W. (1989) Influence of Life-Prolonging Food Restriction on Membrane Lipoperoxidation and Antioxidant Status, in Oxygen Radicals in Biology and Medicine (Simic, G.M., Taylor, K.A., Ward, J.F., and Von Sonntag, C., eds.), pp. 1067–1073, Plenum Press, New York.
Yu, B.P., Suescun, E.A., and Yang, S.Y. (1992) Effect of Age-Related Lipid Peroxidation on Membrane Fluidity and Phospholipase A2: Modulation by Dietary Restriction, Mech. Ageing Dev. 65, 17–23.
Brenner, R.R. (1984) Effect of Unsaturated Fatty Acids on Membrane Structure and Enzyme Kinetics, Progr. Lipid Res. 23, 69–96.
Yeagle, P.L. (1989) Lipid Regulation of Cell Membrane Structure and Function, FASEB J. 3, 1833–1842.
Lee, A.G. (1991) Lipids and Their Effects on Membrane Proteins: Evidence Against a Role for Fluidity, Prog. Lipid Res. 30, 323–348.
Author information
Authors and Affiliations
About this article
Cite this article
Portero-Otín, M., Josep Bellumunt, M., Cristina Ruiz, M. et al. Correlation of fatty acid unsaturation of the major liver mitochondrial phospholipid classes in mammals to their maximum life span potential. Lipids 36, 491–498 (2001). https://doi.org/10.1007/s11745-001-0748-y
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-001-0748-y