Improved motor and cognitive performance with sodium nitrite supplementation is related to small metabolite signatures: A pilot trial in middle-aged and older adults

Aging

Volumn 7, Issue 11, 2015, Pages 1004-1021

  Justice, Jamie N ^a   Johnson, Lawrence C ^a   DeVan, Allison E ^a   Cruickshank Quinn, Charmion ^b   Reisdorph, Nichole ^b   Bassett, Candace J ^a   Evans, Trent D ^a   Brooks, Forrest A ^a   Bryan, Nathan S ^c   Chonchol, Michel B ^d   Giordano, Tony ^e   McQueen, Matthew B ^a   Seals, Douglas R ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b NATIONAL JEWISH MEDICAL AND RESEARCH CENTER   (United States)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

^d UNIVERSITY OF COLORADO   (United States)

^e TheraVasc Inc   (United States)

Author keywords

Aging; Metabolomics; Neuromuscular; Nitrates nitrites; Precision medicine

Indexed keywords

SODIUM NITRITE;

AGED; BLOOD; COGNITION; DIETARY SUPPLEMENT; DRUG EFFECTS; FEMALE; HUMAN; MALE; METABOLOME; MIDDLE AGED; MOTOR ACTIVITY; PILOT STUDY;

AGED; COGNITION; DIETARY SUPPLEMENTS; FEMALE; HUMANS; MALE; METABOLOME; MIDDLE AGED; MOTOR ACTIVITY; PILOT PROJECTS; SODIUM NITRITE;

EID: 84949993634     PISSN: 19454589     EISSN: None     Source Type: Journal    
DOI: 10.18632/aging.100842     Document Type: Article

References (99)

1. Reuben DB, Magasi S, McCreath HE, Bohannon RW, Wang YC, Bubela DJ, Rymer WZ, Beaumont J, Rine RM, Lai JS and Gershon RC. Motor assessment using the NIH Toolbox. Neurology. 2013; 80:S65-75.
2. Marmon AR, Pascoe MA, Schwartz RS and Enoka RM. Associations among strength, steadiness, and hand function across the adult life span. Med Sci Sports Exerc. 2011; 43:560-567.
3. Reid KF and Fielding RA. Skeletal muscle power: a critical determinant of physical functioning in older adults. Exerc Sport Sci Rev. 2012; 40:4-12.
4. Fried LP and Guralnik JM. Disability in older adults: evidence regarding significance, etiology, and risk. J Am Geriatr Soc. 1997; 45:92-100.
5. Ferrucci L, Harris TB, Guralnik JM, Tracy RP, Corti MC, Cohen HJ, Penninx B, Pahor M, Wallace R and Havlik RJ. Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc. 1999; 47:639-646.
6. Rantanen T, Guralnik JM, Foley D, Masaki K, Leveille S, Curb JD and White L. Midlife hand grip strength as a predictor of old age disability. JAMA. 1999; 281:558-560.
7. Cho BL, Scarpace D and Alexander NB. Tests of stepping as indicators of mobility, balance, and fall risk in balance-impaired older adults. J Am Geriatr Soc. 2004; 52:1168-1173.
8. Seals DR, Justice JN and LaRocca TJ. Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol. 2015;10.1113/jphysiol.2014.282665.
9. Olshansky SJ, Goldman DP, Zheng Y and Rowe JW. Aging in America in the twenty-first century: demographic forecasts from the MacArthur Foundation Research Network on an Aging Society. The Milbank quarterly. 2009; 87:842-862.
10. Manton KG, Gu XL, Ullian A, Tolley HD, Headen AE, Jr. and Lowrimore G. Long-term economic growth stimulus of human capital preservation in the elderly. Proc Natl Acad Sci U S A. 2009; 106:21080-21085.
11. Seals DR, Desouza CA, Donato AJ and Tanaka H. Habitual exercise and arterial aging. J Appl Physiol. 2008; 105:1323-1332.
12. Booth FW and Zwetsloot KA. Basic concepts about genes, inactivity and aging. Scand J Med Sci Sports. 2010; 20:1-4.
13. Westerterp KR and Meijer EP. Physical activity and parameters of aging: a physiological perspective. J Gerontol A Biol Sci Med Sci. 2001; 56 Spec No 2:7-12.
14. Paterson DH and Warburton DE. Physical activity and functional limitations in older adults: a systematic review related to Canada's Physical Activity Guidelines. The international journal of behavioral nutrition and physical activity. 2010; 7:38.
15. Paterson DH, Jones GR and Rice CL. Ageing and physical activity: evidence to develop exercise recommendations for older adults. Can J Public Health. 2007; 98 Suppl 2:S69-108.
16. Bailey SJ, Winyard P, Vanhatalo A, Blackwell JR, Dimenna FJ, Wilkerson DP, Tarr J, Benjamin N and Jones AM. Dietary nitrate supplementation reduces the O2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans. J Appl Physiol. 2009; 107:1144-1155.
17. Bailey SJ, Fulford J, Vanhatalo A, Winyard PG, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N and Jones AM. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol. 2010; 109:135-148.
18. Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Gilchrist M, Benjamin N and Jones AM. Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J Appl Physiol. 2011; 110:591-600.
19. Larsen FJ, Weitzberg E, Lundberg JO and Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007; 191:59-66.
20. Larsen FJ, Schiffer TA, Borniquel S, Sahlin K, Ekblom B, Lundberg JO and Weitzberg E. Dietary inorganic nitrate improves mitochondrial efficiency in humans. Cell Metab. 2011; 13:149-159.
21. Justice JN, Gioscia-Ryan RA, Johnson LC, Battson ML, de Picciotto NE, Beck HJ, Jiang H, Sindler AL, Bryan NS, Enoka RM and Seals DR. Sodium nitrite supplementation improves motor function and skeletal muscle inflammatory profile in old male mice. J Appl Physiol (1985). 2015; 118:163-169.
22. LaRoche DP, Greenleaf BL, Croce RV and McGaughy JA. Interaction of age, cognitive function, and gait performance in 50-80-year-olds. Age (Dordr). 2014; 36:9693.
23. Gale CR, Allerhand M, Sayer AA, Cooper C and Deary IJ. The dynamic relationship between cognitive function and walking speed: the English Longitudinal Study of Ageing. Age (Dordr). 2014; 36:9682.
24. Paul V and Ekambaram P. Involvement of nitric oxide in learning & memory processes. Indian J Med Res. 2011; 133:471-478.
25. DeVan AE, Johnson LC, Brooks FA, Evans TD, Justice JN, Cruickshank-Quinn C, Reisdorph N, Bryan NS, McQueen MB, Santos-Parker JR, Chonchol MB, Bassett CJ, Sindler AL, Giordano T, Seals DR. Effects of sodium nitrite supplementation on vascular function and related small metabolite signatures in middle-aged and older adults. J Appl Physiol. 2015; 10.1152/japplphysiol.00879.2015.
26. Shiva S, Huang Z, Grubina R, Sun J, Ringwood LA, MacArthur PH, Xu X, Murphy E, Darley-Usmar VM and Gladwin MT. Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res. 2007; 100:654-661.
27. Vestergaard S, Patel KV, Bandinelli S, Ferrucci L and Guralnik JM. Characteristics of 400-meter walk test performance and subsequent mortality in older adults. Rejuvenation Res. 2009; 12:177-184.
28. Bischoff HA, Stahelin HB, Monsch AU, Iversen MD, Weyh A, von Dechend M, Akos R, Conzelmann M, Dick W and Theiler R. Identifying a cut-off point for normal mobility: a comparison of the timed 'up and go' test in community-dwelling and institutionalised elderly women. Age Ageing. 2003; 32:315-320.
29. Coggan AR, Leibowitz JL, Kadkhodayan A, Thomas DP, Ramamurthy S, Spearie CA, Waller S, Farmer M and Peterson LR. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide. 2014.
30. Izquierdo M, Aguado X, Gonzalez R, Lopez JL and Hakkinen K. Maximal and explosive force production capacity and balance performance in men of different ages. Eur J Appl Physiol Occup Physiol. 1999; 79:260-267.
31. Thompson BJ, Ryan ED, Sobolewski EJ, Conchola EC and Cramer JT. Age related differences in maximal and rapid torque characteristics of the leg extensors and flexors in young, middleaged and old men. Exp Gerontol. 2013; 48:277-282.
32. Bento PC, Pereira G, Ugrinowitsch C and Rodacki AL. Peak torque and rate of torque development in elderly with and without fall history. Clin Biomech (Bristol, Avon). 2010; 25:450-454.
33. Bojsen-Møller J, Magnusson SP, Rasmussen LR, Kjaer M and Aagaard P. Muscle performance during maximal isometric and dynamic contractions is influenced by the stiffness of the tendinous structures. Journal of Applied Physiology. 2005; 99:986-994.
34. Thompson BJ, Ryan ED and Sobolewski EJ. The influence of occupation and age on maximal and rapid lower extremity strength. Applied ergonomics. 2015; 50:62-67.
35. Ng AV and Kent-Braun JA. Slowed muscle contractile properties are not associated with a decreased EMG/force relationship in older humans. J Gerontol A Biol Sci Med Sci. 1999; 54:B452-458.
36. Roos MR, Rice CL, Connelly DM and Vandervoort AA. Quadriceps muscle strength, contractile properties, and motor unit firing rates in young and old men. Muscle Nerve. 1999; 22:1094-1103.
37. Klass M, Baudry S and Duchateau J. Age-related decline in rate of torque development is accompanied by lower maximal motor unit discharge frequency during fast contractions. J Appl Physiol (1985). 2008; 104:739-746.
38. Amodio P, Wenin H, Del Piccolo F, Mapelli D, Montagnese S, Pellegrini A, Musto C, Gatta A and Umilta C. Variability of trail making test, symbol digit test and line trait test in normal people. A normative study taking into account age-dependent decline and sociobiological variables. Aging Clin Exp Res. 2002; 14:117-131.
39. Tombaugh TN. Trail Making Test A and B: normative data stratified by age and education. Archives of clinical neuropsychology: the official journal of the National Academy of Neuropsychologists. 2004; 19:203-214.
40. Greenlief CL, Margolis RB and Erker GJ. Application of the Trail Making Test in differentiating neuropsychological impairment of elderly persons. Percept Mot Skills. 1985; 61:1283-1289.
41. Medell JL and Alexander NB. A clinical measure of maximal and rapid stepping in older women. J Gerontol A Biol Sci Med Sci. 2000; 55:M429-433.
42. Gilchrist M, Winyard PG, Fulford J, Anning C, Shore AC and Benjamin N. Dietary nitrate supplementation improves reaction time in type 2 diabetes: development and application of a novel nitrate-depleted beetroot juice placebo. Nitric Oxide. 2014; 40:67-74.
43. Kelly J, Fulford J, Vanhatalo A, Blackwell JR, French O, Bailey SJ, Gilchrist M, Winyard PG and Jones AM. Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults. Am J Physiol Regul Integr Comp Physiol. 2013; 304:R73-83.
44. Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014; 44 Suppl 1:S35-45.
45. Larsen FJ, Weitzberg E, Lundberg JO and Ekblom B. Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise. Free Radic Biol Med. 2010; 48:342-347.
46. Jan MH, Chai HM, Lin YF, Lin JC, Tsai LY, Ou YC and Lin DH. Effects of age and sex on the results of an ankle plantar-flexor manual muscle test. Phys Ther. 2005; 85:1078-1084.
47. Doherty TJ. Invited review: Aging and sarcopenia. J Appl Physiol. 2003; 95:1717-1727.
48. Enoka RM, Christou EA, Hunter SK, Kornatz KW, Semmler JG, Taylor AM and Tracy BL. Mechanisms that contribute to differences in motor performance between young and old adults. J Electromyogr Kinesiol. 2003; 13:1-12.
49. Vandervoort AA. Aging of the human neuromuscular system. Muscle Nerve. 2002; 25:17-25.
50. Chiueh CC. Neuroprotective properties of nitric oxide. Ann N Y Acad Sci. 1999; 890:301-311.
51. Dawson VL and Dawson TM. Nitric oxide in neurodegeneration. Prog Brain Res. 1998; 118:215-229.
52. Contestabile A, Monti B and Polazzi E. Neuronal-glial Interactions Define the Role of Nitric Oxide in Neural Functional Processes. Curr Neuropharmacol. 2012; 10:303-310.
53. Girouard H and Iadecola C. Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol (1985). 2006; 100:328-335.
54. Fernando MS, Ince PG, Function MRCC and Ageing Neuropathology Study G. Vascular pathologies and cognition in a population-based cohort of elderly people. J Neurol Sci. 2004; 226:13-17.
55. Sindler AL, Fleenor BS, Calvert JW, Marshall KD, Zigler ML, Lefer DJ and Seals DR. Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging. Aging Cell. 2011; 10:429-437.
56. Celsis P, Agniel A, Cardebat D, Demonet JF, Ousset PJ and Puel M. Age related cognitive decline: a clinical entity? A longitudinal study of cerebral blood flow and memory performance. J Neurol Neurosurg Psychiatry. 1997; 62:601-608.
57. Aamand R, Ho YC, Dalsgaard T, Roepstorff A and Lund TE. Dietary nitrate facilitates an acetazolamide-induced increase in cerebral blood flow during visual stimulation. J Appl Physiol (1985). 2014; 116:267-273.
58. Lesniewski LA, Durrant JR, Connell ML, Folian BJ, Donato AJ and Seals DR. Salicylate Treatment Improves Age-Associated Vascular Endothelial Dysfunction: Potential Role of Nuclear Factor κB and Forkhead Box O Phosphorylation. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2011; 66:409-18.
59. Justice JN, Gioscia-Ryan RA, Johnson LC, Battson ML, de Picciotto NE, Beck HJ, Jiang H, Sindler AL, Bryan NS, Enoka RM and Seals DR. Sodium nitrite supplementation improves motor function and skeletal muscle inflammatory profile in old male mice. Journal of applied physiology (Bethesda, Md: 1985). 2014.
60. Blain H, Jaussent A, Beziat S, Dupuy AM, Bernard PL, Mariano-Goulart D, Cristol JP, Sultan C and Picot MC. Low serum IL-6 is associated with high 6-minute walking performance in asymptomatic women aged 20 to 70years. Exp Gerontol. 2012; 47:143-148.
61. Teunissen C, Van Boxtel M, Bosma H, Bosmans E, Delanghe J, De Bruijn C, Wauters A, Maes M, Jolles J and Steinbusch H. Inflammation markers in relation to cognition in a healthy aging population. Journal of neuroimmunology. 2003; 134:142-150.
62. Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, Tylavsky FA and Newman AB. The metabolic syndrome, inflammation, and risk of cognitive decline. Jama. 2004; 292:2237-2242.
63. Bryan NS. Nitrite in nitric oxide biology: Cause or consequence?: A systems-based review. Free Radical Biology and Medicine. 2006; 41:691-701.
64. Barderas MG, Laborde CM, Posada M, de la Cuesta F, Zubiri I, Vivanco F and Alvarez-Llamas G. Metabolomic profiling for identification of novel potential biomarkers in cardiovascular diseases. BioMed Research International. 2011; 2011:790132.
65. Boccard J, Veuthey JL and Rudaz S. Knowledge discovery in metabolomics: an overview of MS data handling. Journal of separation science. 2010; 33:290-304.
66. Lustgarten MS, Price LL, Chalé A and Fielding RA. Metabolites related to gut bacterial metabolism, peroxisome proliferator-activated receptor-alpha activation, and insulin sensitivity are associated with physical function in functionally-limited older adults. Aging cell. 2014; 13:918-925.
67. Shah S, Crosslin D, Haynes C, Nelson S, Turer C, Stevens R, Muehlbauer M, Wenner B, Bain J and Laferrere B. Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Diabetologia. 2012; 55:321-330.
68. Laferrère B, Reilly D, Arias S, Swerdlow N, Gorroochurn P, Bawa B, Bose M, Teixeira J, Stevens RD and Wenner BR. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Science translational medicine. 2011; 3:80re2.
69. Kim S, Cheon H-S, Song J-C, Yun S-M, Park SI and Jeon J-P. Aging-related Changes in Mouse Serum Glycerophospholipid Profiles. Osong public health and research perspectives. 2014; 5:345-350.
70. Lee ES, Soliman KF and Charlton CG. Lysophosphatidylcholine decreases locomotor activities and dopamine turnover rate in rats. Neurotoxicology. 2005; 26:27-38.
71. Lee SH, Park S, Kim H and Jung BH. Metabolomic approaches to the normal aging process. Metabolomics. 2014; 10:1268-1292.
72. Zou Y, Kim DH, Jung KJ, Heo HS, Kim CH, Baik HS, Yu BP, Yokozawa T and Chung HY. Lysophosphatidylcholine enhances oxidative stress via the 5-lipoxygenase pathway in rat aorta during aging. Rejuvenation Res. 2009; 12:15-24.
73. Sevastou I, Kaffe E, Mouratis M-A and Aidinis V. Lysoglycerophospholipids in chronic inflammatory disorders: the PLA 2/LPC and ATX/LPA axes. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 2013; 1831:42-60.
74. Ahmad S, Shahab U, Baig MH, Khan MS, Khan MS, Srivastava AK, Saeed M and Moinuddin. Inhibitory effect of metformin and pyridoxamine in the formation of early, intermediate and advanced glycation end-products. PLoS One. 2013; 8:e72128.
75. Bender A, Beckers J, Schneider I, Holter SM, Haack T, Ruthsatz T, Vogt-Weisenhorn DM, Becker L, Genius J, Rujescu D, Irmler M, Mijalski T, Mader M, et al. Creatine improves health and survival of mice. Neurobiol Aging. 2008; 29:1404-1411.
76. Ferreira LF, Moylan JS, Gilliam LA, Smith JD, Nikolova-Karakashian M and Reid MB. Sphingomyelinase stimulates oxidant signaling to weaken skeletal muscle and promote fatigue. Am J Physiol Cell Physiol. 2010; 299:C552-560.
77. Nixon GF. Sphingolipids in inflammation: pathological implications and potential therapeutic targets. Br J Pharmacol. 2009; 158:982-993.
78. Capuron L, Schroecksnadel S, Feart C, Aubert A, Higueret D, Barberger-Gateau P, Laye S and Fuchs D. Chronic low-grade inflammation in elderly persons is associated with altered tryptophan and tyrosine metabolism: role in neuropsychiatric symptoms. Biol Psychiatry. 2011; 70:175-182.
79. Krauss RM, Zhu H and Kaddurah-Daouk R. Pharmacometabolomics of statin response. Clinical Pharmacology & Therapeutics. 2013; 94:562-565.
80. Ji Y, Hebbring S, Zhu H, Jenkins GD, Biernacka J, Snyder K, Drews M, Fiehn O, Zeng Z and Schaid D. Glycine and a Glycine Dehydrogenase (GLDC) SNP as Citalopram/Escitalopram Response Biomarkers in Depression: Pharmacometabolomics-Informed Pharmacogenomics. Clinical Pharmacology & Therapeutics. 2011; 8997-104.
81. Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, Sinelnikov I, Krishnamurthy R, Eisner R, Gautam B, Young N, Xia J, Knox C, et al. The human serum metabolome. PLoS One. 2011; 6:e16957.
82. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, et al. HMDB 3.0-The Human Metabolome Database in 2013 Nucleic Acids Res. 2013; 41:D801-807.
83. Kohrt WM. Preliminary evidence that DEXA provides an accurate assessment of body composition. J Appl Physiol (1985). 1998; 84:372-377.
84. DeSouza CA, Shapiro LF, Clevenger CM, Dinenno FA, Monahan KD, Tanaka H and Seals DR. Regular aerobic exercise prevents and restores age-related declines in endotheliumdependent vasodilation in healthy men. Circulation. 2000; 102:1351-1357.
85. Justice JN, Pierpoint LA, Mani D, Schwartz R and Enoka RM. Motor function is associated with 1,25(OH)2D and indices of insulin-glucose dynamics in non-diabetic older adults Aging-Clinical and Experimental Research. 2014;26:249-54.
86. Jiang H, Parthasarathy D, Torregrossa AC, Mian A and Bryan NS. Analytical techniques for assaying nitric oxide bioactivity. J Vis Exp. 2012; 64:e3722.
87. Justice JN, Mani D, Pierpoint LA and Enoka RM. Fatigability of the dorsiflexors and associations among multiple domains of motor function in young and old adults. Exp Gerontol. 2014; 55:92-101.
88. Rudroff T, Justice JN, Matthews S, Zuo R and Enoka RM. Muscle activity differs with load compliance during fatiguing contractions with the knee extensor muscles. Experimental brain research Experimentelle Hirnforschung Experimentation cerebrale. 2010; 203:307-316.
89. Lunsford BR and Perry J. The standing heel-rise test for ankle plantar flexion: criterion for normal. Phys Ther. 1995; 75:694-698.
90. Vestergaard S, Nayfield SG, Patel KV, Eldadah B, Cesari M, Ferrucci L, Ceresini G and Guralnik JM. Fatigue in a representative population of older persons and its association with functional impairment, functional limitation, and disability. J Gerontol A Biol Sci Med Sci. 2009; 6476-82.
91. Justice JN, Pierpoint LA, Mani D, Schwartz RS and Enoka RM. Motor function is associated with 1,25(OH)(2)D and indices of insulin-glucose dynamics in non-diabetic older adults. Aging Clin Exp Res. 2014; 26:249-254.
92. Podsiadlo D and Richardson S. The timed "Up & Go": a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991; 39:142-148.
93. Strauss E, Sherman EMS and Spreen O. A compendium of neuropsychological tests: administration, norms and commentary. 2006. (New York: Oxford University Press).
94. Matyash V, Liebisch G, Kurzchalia TV, Shevchenko A and Schwudke D. Lipid extraction by methyl-tert-butyl ether for highthroughput lipidomics. J Lipid Res. 2008; 49:1137-1146.
95. Ruiz-Gutierrez V and Perez-Camino MC. Update on solidphase extraction for the analysis of lipid classes and related compounds. J Chromatogr A. 2000; 885:321-341.
96. Yang Y, Cruickshank C, Armstrong M, Mahaffey S, Reisdorph R and Reisdorph N. New sample preparation approach for mass spectrometry-based profiling of plasma results in improved coverage of metabolome. J Chromatogr A. 2013; 1300C:217-226.
97. Bahr TM, Hughes GJ, Armstrong M, Reisdorph R, Coldren CD, Edwards MG, Schnell C, Kedl R, Laflamme DJ, Reisdorph N, Kechris KJ and Bowler RP. Peripheral blood mononuclear cell gene expression in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2013; in press.
98. Reisdorph N, Mahaffey S, Bowler R, Petrache I, Reisdorph R, Armstrong M, Hughes G and Kechris K. Translational metabolomics and genomics for chronic obstructive pulmonary disease (COPD): Discovering a promising role for sphingolipids. American Thoracic Society and Metabolomics Society Meetings. 2012; A6831.
99. Cruickshank-Quinn CI, Mahaffey S, Justice MJ, Hughes G, Armstrong M, Bowler RP, Reisdorph R, Petrache I and Reisdorph N. Transient and Persistent Metabolomic Changes in Plasma following Chronic Cigarette Smoke Exposure in a Mouse Model. PLoS ONE. 2014; 9:e101855.