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Lipidomics in longevity and healthy aging

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Abstract

The role of classical lipids in aging diseases and human longevity has been widely acknowledged. Triglyceride and cholesterol concentrations are clinically assessed to infer the risk of cardiovascular disease while larger lipoprotein particle size and low triglyceride levels have been identified as markers of human longevity. The rise of lipidomics as a branch of metabolomics has provided an additional layer of accuracy to pinpoint specific lipids and its association with aging diseases and longevity. The molecular composition and concentration of lipid species determine their cellular localization, metabolism, and consequently, their impact in disease and health. For example, low density lipoproteins are the main carriers of sphingomyelins and ceramides, while high density lipoproteins are mostly loaded with ether phosphocholines, partly explaining their opposing roles in atherogenesis. Moreover, the identification of specific lipid species in aging diseases and longevity would aid to clarify how these lipids alter health and influence longevity. For instance, ether phosphocholines PC (O-34:1) and PC (O-34:3) have been positively associated with longevity and negatively with diabetes, and hypertension, but other species of phosphocholines show no effect or an opposite association with these traits confirming the relevance of the identification of molecular lipid species to tackle our understanding of healthy aging and disease. Up-to-date, a minor fraction of the human plasma lipidome has been associated to healthy aging and longevity, further research would pinpoint toward specific lipidomic profiles as potential markers of healthy aging and metabolic diseases.

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References

  • Abbott SK, Else PL et al (2012) Fatty acid composition of membrane bilayers: importance of diet polyunsaturated fat balance. Biochim Biophys Acta 1818(5):1309–1317

    Article  PubMed  CAS  Google Scholar 

  • Altmaier E, Kastenmüller G et al (2009) Variation in the human lipidome associated with coffee consumption as revealed by quantitative targeted metabolomics. Mol Nutr Food Res 53(11):1357–1365

    Article  PubMed  CAS  Google Scholar 

  • Atzmon G, Schechter C et al (2004) Clinical phenotype of families with longevity. J Am Geriatr Soc 52(2):274–277

    Article  PubMed  Google Scholar 

  • Atzmon G, Rincon M et al (2006) Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 4(4):e113

    Article  PubMed  Google Scholar 

  • Atzmon G, Pollin T et al (2008) Adiponectin levels and genotype: a potential regulator of life span in humans. J Gerontol A Biol Sci Med Sci 63(5):447–453

    Article  PubMed  Google Scholar 

  • Barzilai N, Gabriely I et al (2001) Offspring of centenarians have a favorable lipid profile. J Am Geriatr Soc 49(1):76–79

    Article  PubMed  CAS  Google Scholar 

  • Barzilai N, Atzmon G et al (2003) Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 290(15):2030–2040

    Article  PubMed  CAS  Google Scholar 

  • Barzilai N, Huffman DM et al (2012) The critical role of metabolic pathways in aging. Diabetes 61(6):1315–1322

    Article  PubMed  CAS  Google Scholar 

  • Beekman M, Blanche H et al (2013) Genome-wide linkage analysis for human longevity: genetics of healthy aging study. Aging Cell 12(2):184–193

    Article  PubMed  CAS  Google Scholar 

  • Bergman A, Atzmon G et al (2007) Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging. PLoS Comput Biol 3(8):e170

    Article  PubMed  Google Scholar 

  • Boullart ACI, de Graaf J et al (2011) Serum triglycerides and risk of cardiovascular disease. Biochim Biophys Acta 1821(5):867–875

    PubMed  Google Scholar 

  • Broer L, Codd V et al (2013) Meta-analysis of telomere length in 19713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect. Eur J Hum Genet. doi:10.1038/ejhg.2012.303

    PubMed  Google Scholar 

  • Budovsky A, Craig T, Wang J, Tacutu R, Csordas A, Lourenço J, Fraifeld VE, de Magalhães JP (2013) LongevityMap: a database of human genetic variants associated with longevity. Trends Genet (accepted)

  • Buffenstein R, Edrey YH et al (2008) The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms. Age 30(2–3):99–109

    Article  PubMed  CAS  Google Scholar 

  • Caprari P, Scuteri A et al (1999) Aging and red blood cell membrane: a study of centenarians. Exp Gerontol 34(1):47–57

    Article  PubMed  CAS  Google Scholar 

  • Cherif H, Tarry JL et al (2003) Ageing and telomeres: a study into organ and gender specific telomere shortening. Nucleic Acids Res 31(5):1576–1583

    Article  PubMed  CAS  Google Scholar 

  • Coen PM, Dubé JJ et al (2010) Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content. Diabetes 59(1):80–88

    Article  PubMed  CAS  Google Scholar 

  • Crimmins EM, Finch CE (2012) The genetics of age-related health outcomes. J Gerontol A Biol Sci Med Sci 67A(5):467–469

    Article  Google Scholar 

  • Deelen J, Beekman M et al (2011) Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited. Aging Cell 10(4):686–698

    Article  PubMed  CAS  Google Scholar 

  • Deelen J, Beekman M et al (2013) Identifying the genomic determinants of aging and longevity in human population studies: progress and challenges. BioEssays 35(4):386–396

    Article  PubMed  CAS  Google Scholar 

  • Dennis EA (2009) Lipidomics joins the omics evolution. Proc Natl Acad Sci USA 106(7):2089–2090

    Article  PubMed  CAS  Google Scholar 

  • Ding N, Nie H et al (2011) Human serum N-glycan profiles are age and sex dependent. Age Ageing 40(5):568–575

    Article  PubMed  Google Scholar 

  • Dowling DK, Simmons LW (2009) Reactive oxygen species as universal constraints in life-history evolution. Proc R Soc B Biol Sci 276(1663):1737–1745

    Article  CAS  Google Scholar 

  • Euser SM, van Heemst D et al (2008) Insulin/insulin-like growth factor-1 signaling and cognitive function in humans. J Gerontol A Biol Sci Med Sci 63(9):907–910

    Article  PubMed  Google Scholar 

  • Fahy E, Subramaniam S et al (2005) A comprehensive classification system for lipids. J Lipid Res 46(5):839–862

    Article  PubMed  CAS  Google Scholar 

  • Freedman ND, Park Y et al (2012) Association of coffee drinking with total and cause-specific mortality. N Engl J Med 366(20):1891–1904

    Article  PubMed  CAS  Google Scholar 

  • Gibellini F, Smith TK (2010) The Kennedy pathway—de novo synthesis of phosphatidylethanolamine and phosphatidylcholine. IUBMB Life 62(6):414–428

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Covarrubias V, Beekman M et al (2013) Lipidomics of familial longevity. Aging Cell 12(3):426–434

    Article  PubMed  CAS  Google Scholar 

  • Graessler J, Schwudke D et al (2009) Top-down lipidomics reveals ether lipid deficiency in blood plasma of hypertensive patients. PLoS ONE 4(7):e6261

    Article  PubMed  Google Scholar 

  • Gross RW, Han X (2011) Lipidomics at the interface of structure and function in systems biology. Chem Biol 18(3):284–291

    Article  PubMed  CAS  Google Scholar 

  • Han X, Rozen S et al (2011) Metabolomics in early Alzheimer’s disease: identification of altered plasma sphingolipidome using shotgun lipidomics. PLoS ONE 6(7):e21643

    Article  PubMed  CAS  Google Scholar 

  • Haus JM, Kashyap SR et al (2009) Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes 58(2):337–343

    Article  PubMed  CAS  Google Scholar 

  • Heijmans BT, Gussekloo J et al (1999) Mortality risk in men is associated with a common mutation in the methylene-tetrahydrofolate reductase gene (MTHFR). Eur J Hum Genet 7(2):197–204

    Article  PubMed  CAS  Google Scholar 

  • Heijmans BT, Beekman M et al (2006) Lipoprotein particle profiles mark familial and sporadic human longevity. PLoS Med 3(12):e495

    Article  PubMed  Google Scholar 

  • Helmy FM, Hack MH et al (2003) Age-related changes of the endogenous cardiolipin and plasmalogens of guinea pig kidney and their in vitro hydrolysis by endogenous phospholipases: a thin layer chromatographic analysis in conjunction with densitometric measurement. Cell Biochem Funct 21(4):337–344

    Article  PubMed  CAS  Google Scholar 

  • Holland WL, Summers SA (2008) Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev 29(4):381–402

    Article  PubMed  CAS  Google Scholar 

  • Hulbert AJ (2003) Life, death and membrane bilayers. J Exp Biol 206(14):2303–2311

    Article  PubMed  CAS  Google Scholar 

  • Hulbert AJ (2005) On the importance of fatty acid composition of membranes for aging. J Theor Biol 234(2):277–288

    Article  PubMed  CAS  Google Scholar 

  • Hulbert AJ (2008) Explaining longevity of different animals: is membrane fatty acid composition the missing link? Age 30(2–3):89–97

    Article  PubMed  CAS  Google Scholar 

  • International Consortium for Blood Pressure Genome-Wide Association Studies and Collaborators (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478(7367):103–109

    Article  Google Scholar 

  • Kamath S, Chavez AO et al (2011) Coordinated defects in hepatic long chain fatty acid metabolism and triglyceride accumulation contribute to insulin resistance in non-human primates. PLoS ONE 6(11):e27617

    Article  PubMed  CAS  Google Scholar 

  • Lie J, Moerland M et al (2006) Sex differences in atherosclerosis in mice with elevated phospholipid transfer protein activity are related to decreased plasma high density lipoproteins and not to increased production of triglycerides. Biochim Biophys Acta 1761(9):1070–1077

    Article  PubMed  CAS  Google Scholar 

  • Lipton RB, Hirsch J et al (2010) Exceptional parental longevity associated with lower risk of Alzheimer’s disease and memory decline. J Am Geriatr Soc 58(6):1043–1049

    Article  PubMed  Google Scholar 

  • Loscalzo J (2013) Gut microbiota, the genome, and diet in atherogenesis. N Engl J Med 368(17):1647–1649

    Article  PubMed  CAS  Google Scholar 

  • Martin GM, Bergman A et al (2007) Genetic determinants of human health span and life span: progress and new opportunities. PLoS Genet 3(7):e125

    Article  PubMed  Google Scholar 

  • Miller M, Stone NJ et al (2011) Triglycerides and cardiovascular disease. Circulation 123(20):2292–2333

    Article  PubMed  Google Scholar 

  • Mitchell BD, Hsueh WC et al (2001) Heritability of life span in the old order Amish. Am J Med Genet 102(4):346–352

    Article  PubMed  CAS  Google Scholar 

  • Mittelstrass K, Ried JS et al (2011) Discovery of sexual dimorphisms in metabolic and genetic biomarkers. PLoS Genet 7(8):e1002215

    Article  PubMed  CAS  Google Scholar 

  • Mittendorfer B (2005) Sexual dimorphism in human lipid metabolism. J Nutr 135(4):681–686

    PubMed  CAS  Google Scholar 

  • Muller FL, Lustgarten MS et al (2007) Trends in oxidative aging theories. Free Radic Biol Med 43(4):477–503

    Article  PubMed  CAS  Google Scholar 

  • Nebel A, Kleindorp R et al (2011) A genome-wide association study confirms APOE as the major gene influencing survival in long-lived individuals. Mech Ageing Dev 132(6–7):324–330

    Article  PubMed  CAS  Google Scholar 

  • Nelson JC, Jiang X-C et al (2006) Plasma sphingomyelin and subclinical atherosclerosis: findings from the multi-ethnic study of atherosclerosis. Am J Epidemiol 163(10):903–912

    Article  PubMed  Google Scholar 

  • Okura T, Koda M et al (2003) Association of polymorphisms in the estrogen receptor a gene with body fat distribution. Int J Obes Relat Metab Disord 27(9):1020

    Article  PubMed  CAS  Google Scholar 

  • Pamplona R, Portero-Otin M et al (2000) Double bond content of phospholipids and lipid peroxidation negatively correlate with maximum longevity in the heart of mammals. Mech Ageing Dev 112(3):169–183

    Article  PubMed  CAS  Google Scholar 

  • Pawlikowska L, Hu D et al (2009) Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell 8(4):460–472

    Article  PubMed  CAS  Google Scholar 

  • Piccinini M, Scandroglio F et al (2010) Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders. Mol Neurobiol 41(2):314–340

    Article  PubMed  CAS  Google Scholar 

  • Pietilainen KH, Sysi-Aho M et al (2007) Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects—a monozygotic twin study. PLoS ONE 2(2):e218

    Article  PubMed  Google Scholar 

  • Portero-Otín M, Josep Bellumunt M et al (2001) Correlation of fatty acid unsaturation of the major liver mitochondrial phospholipid classes in mammals to their maximum life span potential. Lipids 36(5):491–498

    Article  PubMed  Google Scholar 

  • Puca AA, Andrew P et al (2007) Fatty acid profile of erythrocyte membranes as possible biomarker of longevity. Rejuvenation Res 11(1):63–72

    Article  Google Scholar 

  • Puca AA, Chatgilialoglu C et al (2008) Lipid metabolism and diet: possible mechanisms of slow aging. Int J Biochem Cell Biol 40(3):324–333

    Article  PubMed  CAS  Google Scholar 

  • Quehenberger O, Dennis EA (2011) The human plasma lipidome. N Engl J Med 365(19):1812–1823

    Article  PubMed  CAS  Google Scholar 

  • Quehenberger O, Armando AM et al (2010) Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res 51(11):3299–3305

    Article  PubMed  CAS  Google Scholar 

  • Rhee EP, Cheng S et al (2011) Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Investig 121(4):1402–1411

    Article  PubMed  CAS  Google Scholar 

  • Rozing MP, Westendorp RGJ et al (2009) Human insulin/IGF-1 and familial longevity at middle age. Aging 1(8):714–722

    PubMed  CAS  Google Scholar 

  • Rozing MP, Westendorp RGJ et al (2010) Favorable glucose tolerance and lower prevalence of metabolic syndrome in offspring without diabetes mellitus of nonagenarian siblings: the Leiden longevity study. J Am Geriatr Soc 58(3):564–569

    Article  PubMed  Google Scholar 

  • Ruhaak LR, Uh H-W et al (2010) Plasma protein N-glycan profiles are associated with calendar age, familial longevity and health. J Proteome Res 10(4):1667–1674

    Article  Google Scholar 

  • Schoenmaker M, de Craen AJM et al (2006) Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden longevity study. Eur J Hum Genet 14:79–84

    PubMed  Google Scholar 

  • Schupf N, Barral S et al (2013) Apolipoprotein E and familial longevity. Neurobiol Aging 34(4):1287–1291

    Article  PubMed  CAS  Google Scholar 

  • Schwartz EA, Reaven PD (2011) Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis. Biochim Biophys Acta 1821(5):858–866

    PubMed  Google Scholar 

  • Sebastiani P, Solovieff N et al (2012) Genetic signatures of exceptional longevity in humans. PLoS ONE 7(1):e29848

    Article  PubMed  CAS  Google Scholar 

  • Slagboom PE, Beekman M et al (2011) Genomics of human longevity. Philos Trans R Soc B Biol Sci 366(1561):35–42

    Article  CAS  Google Scholar 

  • Soerensen M, Dato S et al (2013) Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity. Age 35(2):487–500

    Article  PubMed  CAS  Google Scholar 

  • Sugiyama MG, Agellon LB (2012) Sex differences in lipid metabolism and metabolic disease risk. Biochem Cell Biol 90(2):124–141

    Article  PubMed  CAS  Google Scholar 

  • Suhre K, Meisinger C et al (2010) Metabolic footprint of diabetes: a multiplatform metabolomics study in an epidemiological setting. PLoS ONE 5(11):e13953

    Article  PubMed  Google Scholar 

  • Tacutu R, Budovsky A, Fraifeld VE (2010) The NetAge database: a compendium of networks for longevity, age-related diseases and associated processes. Biogerontology 11(4):513–522

    Google Scholar 

  • Vaarhorst A, Beekman M et al (2011) Lipid metabolism in long-lived families: the Leiden longevity study. Age 33(2):219–227

    Article  PubMed  CAS  Google Scholar 

  • van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom P, Westendorp RGJ (2005) Reduced insulin/IGF-1 signalling and human longevity. Aging Cell 4(2):79–85

    Article  PubMed  Google Scholar 

  • Viviani Anselmi C, Ferreri C et al (2010) Fatty acid percentage in erythrocyte membranes of atrial flutter/fibrillation patients and controls. J Interv Card Electrophysiol 27(2):95–99

    Article  PubMed  Google Scholar 

  • Wang X, Magkos F et al (2011) Sex differences in lipid and lipoprotein metabolism: it’s not just about sex hormones. J Clin Endocrinol Metab 96(4):885–893

    Article  PubMed  CAS  Google Scholar 

  • Wang-Sattler R, Yu Z et al (2012) Novel biomarkers for pre-diabetes identified by metabolomics. Mol Syst Biol 8:615

    Article  PubMed  Google Scholar 

  • Westendorp RGJ, van Heemst D et al (2009) Nonagenarian siblings and their offspring display lower risk of mortality and morbidity than sporadic nonagenarians: the Leiden longevity study. J Am Geriatr Soc 57(9):1634–1637

    Article  PubMed  Google Scholar 

  • Wiesner P, Leidl K et al (2009) Lipid profiling of FPLC-separated lipoprotein fractions by electrospray ionization tandem mass spectrometry. J Lipid Res 50(3):574–585

    Article  PubMed  CAS  Google Scholar 

  • Yasmeen R, Reichert B et al (2013) Autocrine function of aldehyde dehydrogenase 1 as a determinant of diet- and sex-specific differences in visceral adiposity. Diabetes 62(1):124–136

    Article  PubMed  CAS  Google Scholar 

  • Yeboah J, McNamara C et al (2010) Association of plasma sphingomyelin levels and incident coronary heart disease events in an adult population. Arterioscler Thromb Vasc Biol 30(3):628–633

    Article  PubMed  CAS  Google Scholar 

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  1. Analytical Biosciences, Leiden University, PO Box 9502, Einsteinweg 55, 2300 RA, Leiden, The Netherlands

    Vanessa Gonzalez-Covarrubias

  2. Instituto Nacional de Medicina Genómica (INMEGEN), Secretaría de Salud, C.P. 01900, México City, Distrito Federal, Mexico

    Vanessa Gonzalez-Covarrubias

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Correspondence to Vanessa Gonzalez-Covarrubias.

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Gonzalez-Covarrubias, V. Lipidomics in longevity and healthy aging. Biogerontology 14, 663–672 (2013). https://doi.org/10.1007/s10522-013-9450-7

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