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Metabolic Biomarkers in Aging and Anti-Aging Research

  • Paul C. Guest
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1178)

Abstract

Although human life expectancy has increased significantly over the last two centuries, this has not been paralleled by a similar rise in healthy life expectancy. Thus, an important goal of anti-aging research has been to reduce the impact of age-associated diseases as a way of extending the human healthspan. This review will explore some of the potential avenues which have emerged from this research as the most promising strategies and drug targets for therapeutic interventions to promote healthy aging.

Keywords

Longevity Lifespan Model organisms C-elegans Mouse Rat Biomarkers 

References

  1. 1.
    Christensen K, Doblhammer G, Rau R, Vaupel JW (2009) Ageing populations: the challenges ahead. Lancet 374(9696):1196–1208CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Kontis V, Bennett JE, Mathers CD, Li G, Foreman K, Ezzati M (2017) Future life expectancy in 35 industrialised countries: projections with a Bayesian model ensemble. Lancet 389(10076):1323–1335CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Boss GR, Seegmiller JE (1981) Age-related physiological changes and their clinical significance. West J Med 135(6):434–440PubMedPubMedCentralGoogle Scholar
  4. 4.
    Rizvi S, Raza ST, Mahdi F (2014) Telomere length variations in aging and age-related diseases. Curr Aging Sci 7(3):161–167CrossRefPubMedGoogle Scholar
  5. 5.
    Melov S (2016) Geroscience approaches to increase healthspan and slow aging. F1000Res 5. pii: F1000 Faculty Rev-785.  https://doi.org/10.12688/f1000research.7583.1CrossRefGoogle Scholar
  6. 6.
    Hansen M, Kennedy BK (2016) Does longer lifespan mean longer healthspan? Trends Cell Biol 26(8):565–568CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Crimmins EM (2015) Lifespan and healthspan: past, present, and promise. Gerontologist 55(6):901–911CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621CrossRefPubMedGoogle Scholar
  9. 9.
    Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75:685–705CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Wang C, Jurk D, Maddick M, Nelson G, Martin-Ruiz C, von Zglinicki T (2009) DNA damage response and cellular senescence in tissues of aging mice. Aging Cell 8(3):311–323CrossRefPubMedGoogle Scholar
  11. 11.
    Leong I (2018) Sustained caloric restriction in health. Nat Rev Endocrinol 14:322.  https://doi.org/10.1038/s41574-018-0008-2CrossRefPubMedGoogle Scholar
  12. 12.
    Redman LM, Smith SR, Burton JH, Martin CK, Il’yasova D, Ravussin E (2018) Metabolic slowing and reduced oxidative damage with sustained caloric restriction support the rate of living and oxidative damage theories of aging. Cell Metab 27(4):805–815.e4CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G et al (2014) The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet. Cell Rep 6(5):836–843CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K et al (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Zinovkin RA, Zamyatnin AA (2018) Mitochondria-targeted drugs. Curr Mol Pharmacol.  https://doi.org/10.2174/1874467212666181127151059. [Epub ahead of print]CrossRefPubMedGoogle Scholar
  16. 16.
    Payne BA, Chinnery PF (2015) Mitochondrial dysfunction in aging: much progress but many unresolved questions. Biochim Biophys Acta 1847(11):1347–1353CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Faitg J, Reynaud O, Leduc-Gaudet JP, Gouspillou G (2017) Skeletal muscle aging and mitochondrial dysfunction: an update. Med Sci (Paris) 33(11):955–962CrossRefGoogle Scholar
  18. 18.
    Hoppel CL, Lesnefsky EJ, Chen Q, Tandler B (2017) Mitochondrial dysfunction in cardiovascular aging. Adv Exp Med Biol 982:451–464CrossRefPubMedGoogle Scholar
  19. 19.
    Morita M, Ikeshima-Kataoka H, Kreft M, Vardjan N, Zorec R, Noda M (2019) Metabolic plasticity of astrocytes and aging of the brain. Int J Mol Sci 20(4). pii: E941.  https://doi.org/10.3390/ijms20040941CrossRefPubMedCentralGoogle Scholar
  20. 20.
    Kim SH, Kim H (2018). Inhibitory effect of astaxanthin on oxidative stress-induced mitochondrial dysfunction-a mini-review. Nutrients 10(9). pii: E1137.  https://doi.org/10.3390/nu10091137CrossRefPubMedCentralGoogle Scholar
  21. 21.
    Son HG, Altintas O, Kim EJE, Kwon S, Lee SV (2019) Age-dependent changes and biomarkers of aging in Caenorhabditis elegans. Aging Cell 18(2):e12853.  https://doi.org/10.1111/acel.12853CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366(6454):461–464CrossRefPubMedGoogle Scholar
  23. 23.
    Kenyon CJ (2010) The genetics of ageing. Nature 464(7288):504–512CrossRefPubMedGoogle Scholar
  24. 24.
    Lakowski B, Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci U S A 95(22):13091–13096CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Fierro-González JC, González-Barrios M, Miranda-Vizuete A, Swoboda P (2011) The thioredoxin TRX-1 regulates adult lifespan extension induced by dietary restriction in Caenorhabditis elegans. Biochem Biophys Res Commun 406(3):478–482CrossRefPubMedGoogle Scholar
  26. 26.
    Hansen M, Hsu AL, Dillin A, Kenyon C (2005) New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 1(1):119–128CrossRefPubMedGoogle Scholar
  27. 27.
    Honda Y, Honda S (2002) Life span extensions associated with upregulation of gene expression of antioxidant enzymes in Caenorhabditis elegans; studies of mutation in the AGE-1, PI3 kinase homologue and short-term exposure to hyperoxia. J Am Aging Assoc 24(1):21–25Google Scholar
  28. 28.
    Yanase S, Yasuda K, Ishii N (2002) Adaptive responses to oxidative damage in three mutants of Caenorhabditis elegans (age-1, mev-1 and daf-16) that affect life span. Mech Ageing Dev 123(12):1579–1587CrossRefPubMedGoogle Scholar
  29. 29.
    Yanase S, Ishii N (2008) Hyperoxia exposure induced hormesis decreases mitochondrial superoxide radical levels via Ins/IGF-1 signaling pathway in a long-lived age-1 mutant of Caenorhabditis elegans. J Radiat Res 49(3):211–218CrossRefPubMedGoogle Scholar
  30. 30.
    Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA et al (1997) The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389(6654):994–999CrossRefPubMedGoogle Scholar
  31. 31.
    Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278(5341):1319–1322CrossRefPubMedGoogle Scholar
  32. 32.
    Kenyon C (2006) Enrichment of regulatory motifs upstream of predicted DAF-16 targets. Nat Genet 38(4):397–398CrossRefPubMedGoogle Scholar
  33. 33.
    Minniti AN, Cataldo R, Trigo C, Vasquez L, Mujica P, Leighton F et al (2009) Methionine sulfoxide reductase A expression is regulated by the DAF-16/FOXO pathway in Caenorhabditis elegans. Aging Cell 8(6):690–705CrossRefPubMedGoogle Scholar
  34. 34.
    Vanfleteren JR (1993) Oxidative stress and ageing in Caenorhabditis elegans. Biochem J 292(Pt 2):605–608CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Murakami S, Johnson TE (1996) A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics 143(3):1207–1218PubMedPubMedCentralGoogle Scholar
  36. 36.
    Van Voorhies WA, Ward S (1999) Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proc Natl Acad Sci U S A 96(20):11399–11403CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Barsyte D, Lovejoy DA, Lithgow GJ (2001) Longevity and heavy metal resistance in daf-2 and age-1 long-lived mutants of Caenorhabditis elegans. FASEB J 15(3):627–634CrossRefGoogle Scholar
  38. 38.
    Shoyama T, Shimizu Y, Suda H (2009) Decline in oxygen consumption correlates with lifespan in long-lived and short-lived mutants of Caenorhabditis elegans. Exp Gerontol 44(12):784–791CrossRefPubMedGoogle Scholar
  39. 39.
    Larsen PL (1993) Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci U S A 90(19):8905–8909CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Wood WB (1988) Introduction to C. elegans biology. In: Wood WB, The Community of C. elegans Researchers (eds) The nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press, New York, pp 1–16. ISBN: 0-87969-433-5Google Scholar
  41. 41.
    Riddle DL (1988) The dauer larva. In: Wood WB, The Community of C. elegans Researchers (eds) The nematode Caenorhabditis elegans. Cold Spring Harbor Laboratory Press, New York, pp 393–412. ISBN: 0-87969-433-5Google Scholar
  42. 42.
    Wadsworth WG, Riddle DL (1989) Developmental regulation of energy metabolism in Caenorhabditis elegans. Dev Biol 132(1):167–173CrossRefPubMedGoogle Scholar
  43. 43.
    Van Voorhies WA, Ward S (2000) Broad oxygen tolerance in the nematode Caenorhabditis elegans. J Biol Chem 203(Pt 16):2467–2478Google Scholar
  44. 44.
    Vanfleteren JR, De Vreese A (1996) Rate of aerobic metabolism and superoxide production rate potential in the nematode Caenorhabditis elegans. J Exp Zool 274(2):93–100CrossRefPubMedGoogle Scholar
  45. 45.
    Klass MR, Johnson TE (1985) Caenorhabditis elegans. In: Lints FA (ed) Non-mammalian models for research on aging. Karger, Basel, pp 164–187. ISBN: 3805540191Google Scholar
  46. 46.
    Chow DK, Glenn CF, Johnston JL, Goldberg IG, Wolkow CA (2006) Sarcopenia in the Caenorhabditis elegans pharynx correlates with muscle contraction rate over lifespan. Exp Gerontol 41(3):252–260CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Yanase S, Suda H, Yasuda K, Ishii N (2017) Impaired p53/CEP-1 is associated with lifespan extension through an age-related imbalance in the energy metabolism of C. elegans. Genes Cells 22(12):1004–1010CrossRefPubMedGoogle Scholar
  48. 48.
    Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277(34):30409–30412CrossRefPubMedGoogle Scholar
  49. 49.
    Yang J, Kalhan SC, Hanson RW (2009) What is the metabolic role of phosphoenolpyruvate carboxykinase? J Biol Chem 284(40):27025–27029CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Rodgers JT, Lerin C, Naas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature 434(7029):113–118CrossRefGoogle Scholar
  51. 51.
    Honda S, Matsuo M (1992) Lifespan shortening of the nematode Caenorhabditis elegans under higher concentrations of oxygen. Mech Ageing Dev 63(3):135–246CrossRefGoogle Scholar
  52. 52.
    Darr D, Fridovich I (1995) Adaptation to oxidative stress in young, but not in mature or old, Caenorhabditis elegans. Free Radic Biol Med 18(2):195–201CrossRefPubMedGoogle Scholar
  53. 53.
    Freeman BA, Crapo JD (1981) Hyperoxia increases oxygen radical production in rat lungs and lung mitochondria. J Biol Chem 256(21):10986–10992PubMedGoogle Scholar
  54. 54.
    Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, Senoo-Matsuda N et al (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394(6694):694–697CrossRefGoogle Scholar
  55. 55.
    Senoo-Matsuda N, Yasuda K, Tsuda M, Ohkubo T, Yoshimura S, Nakazawa H et al (2001) A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans. J Biol Chem 276(45):41553–41558CrossRefPubMedGoogle Scholar
  56. 56.
    DiMauro S, Schon EA (2003) Mitochondrial respiratory-chain diseases. N Engl J Med 348(26):2656–2568CrossRefPubMedGoogle Scholar
  57. 57.
    Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300CrossRefGoogle Scholar
  58. 58.
    Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20(4):145–147CrossRefPubMedGoogle Scholar
  59. 59.
    Dai D-F, Chiao Y-A, Martin GM, Marcinek DJ, Basisty N, Quarles EK et al (2017) Mitochondrial-targeted catalase: extended longevity and the roles in various disease models. Prog Mol Biol Transl Sci 146:203–241CrossRefPubMedGoogle Scholar
  60. 60.
    Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911CrossRefGoogle Scholar
  61. 61.
    Li D, Lai Y, Yue Y, Rabinovitch PS, Hakim C, Duan D (2009) Ectopic catalase expression in mitochondria by adeno-associated virus enhances exercise performance in mice. In: Lucia A (ed). PLoS One 4:e6673.  https://doi.org/10.1371/journal.pone.0006673CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Selsby JT (2011) Increased catalase expression improves muscle function in mdx mice. Exp Physiol 96(2):194–202CrossRefPubMedGoogle Scholar
  63. 63.
    Azadmanesh J, Borgstahl GEO (2018) A review of the catalytic mechanism of human manganese superoxide dismutase. Antioxidants (Basel, Switzerland) 7:25.  https://doi.org/10.3390/antiox7020025CrossRefGoogle Scholar
  64. 64.
    Zhou R-H, Vendrov AE, Tchivilev I, Niu X-L, Molnar KC, Rojas M et al (2012) Mitochondrial oxidative stress in aortic stiffening with age: the role of smooth muscle cell function. Arterioscler Thromb Vasc Biol 32(3):745–755CrossRefPubMedGoogle Scholar
  65. 65.
    Salminen LE, Schofield PR, Pierce KD, Bruce SE, Griffin MG, Tate DF et al (2017) Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: a preliminary study of antioxidant defense genes in brain aging. Behav Brain Res 329:111–119CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Ernster L, Dallner G (1995) Biochemical, physiological and medical aspects of ubiquinone function. Biochim Biophys Acta 1271(1):195–204CrossRefGoogle Scholar
  67. 67.
    Hernández-Camacho JD, Bernier M, López-Lluch G, Navas P (2018) Coenzyme Q10 supplementation in aging and disease. Front Physiol 9:44.  https://doi.org/10.3389/fphys.2018.00044CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Shetty RA, Forster MJ, Sumien N (2013) Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age (Dordr) 35(5):1821–1834CrossRefGoogle Scholar
  69. 69.
    Ulla A, Mohamed MK, Sikder B, Rahman AT, Sumi FA, Hossain M et al (2017) Coenzyme Q10 prevents oxidative stress and fibrosis in isoprenaline induced cardiac remodeling in aged rats. BMC Pharmacol Toxicol 18:29.  https://doi.org/10.1186/s40360-017-0136-7CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    McManus MJ, Murphy MP, Franklin JL (2011) The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease. J Neurosci 31(44):15703–15715CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Ng LF, Gruber J, Cheah IK, Goo CK, Cheong WF, Shui G et al (2014) The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease. Free Radic Biol Med 71:390–401CrossRefPubMedGoogle Scholar
  72. 72.
    Betz C, Hall MN (2013) Where is mTOR and what is it doing there? J Cell Biol 203(4):563–574CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Fontana L, Partridge L, Longo VD (2010) Extending healthy life span--from yeast to humans. Science 328(5976):321–326CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW-L, Thomas EL et al (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11(6):453–465CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Lamming DW, Ye L, Sabatini DM, Baur JA (2013) Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest 123(3):980–989CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Xia Y, Sun M, Xie Y, Shu R (2017) mTOR inhibition rejuvenates the aging gingival fibroblasts through alleviating oxidative stress. Oxid Med Cell Longev 2017:6292630.  https://doi.org/10.1155/2017/6292630CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Araki T, Sasaki Y, Milbrandt J (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305(5686):1010–1013CrossRefPubMedGoogle Scholar
  78. 78.
    Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B et al (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305(5682):390–392CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Nemoto S, Fergusson MM, Finkel T (2004) Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 306(5704):2105–2108CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Bordone L, Motta MC, Picard F, Robinson A, Jhala US, Apfeld J et al (2006) Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. In: Dillin A (ed). PLoS Biol 4:e31.  https://doi.org/10.1371/journal.pbio.0040031CrossRefPubMedGoogle Scholar
  81. 81.
    Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim S-H, Mostoslavsky R et al (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 26(7):1913–1923CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P (2008) Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett 582(1):46–53CrossRefPubMedGoogle Scholar
  83. 83.
    Ramis MR, Esteban S, Miralles A, Tan D-X, Reiter RJ (2015) Caloric restriction, resveratrol and melatonin: role of SIRT1 and implications for aging and related-diseases. Mech Ageing Dev 146–148:28–41CrossRefPubMedGoogle Scholar
  84. 84.
    Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C et al (2010) Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143(5):802–812CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES, Boersma MD et al (2013) Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol Cell 49(1):186–199CrossRefPubMedGoogle Scholar
  86. 86.
    Pérez H, Finocchietto PV, Alippe Y, Rebagliati I, Elguero ME, Villalba N et al (2018) p66Shc inactivation modifies RNS production, regulates Sirt3 activity, and improves mitochondrial homeostasis, delaying the aging process in mouse brain. Oxid Med Cell Longev 2018:8561892.  https://doi.org/10.1155/2018/8561892CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Li Y, Ma Y, Song L, Yu L, Zhang L, Zhang Y et al (2018) SIRT3 deficiency exacerbates p53/Parkin-mediated mitophagy inhibition and promotes mitochondrial dysfunction: implication for aged hearts. Int J Mol Med 41(6):3517–3526PubMedGoogle Scholar
  88. 88.
    Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM et al (2006) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325(5937):201–204CrossRefGoogle Scholar
  89. 89.
    Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM (2014) Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5:3557.  https://doi.org/10.1038/ncomms4557CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Witte AV, Fobker M, Gellner R, Knecht S, Flöel A (2009) Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 106(4):1255–1260CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Aw TY (1991) Postnatal changes in pyridine nucleotides in rat hepatocytes: composition and O2 dependence. Pediatr Res 30(1):112–117CrossRefPubMedGoogle Scholar
  92. 92.
    Ghosh D, Levault KR, Brewer GJ (2014) Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons. Aging Cell 13(4):631–640CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Lenaz G, D’Aurelio M, Merlo Pich M, Genova ML, Ventura B, Bovina C et al (2000) Mitochondrial bioenergetics in aging. Biochim Biophys Acta 1459(2–3):397–404CrossRefPubMedGoogle Scholar
  94. 94.
    Baciou L, Masoud R, Souabni H, Serfaty X, Karimi G, Bizouarn T et al (2018) Phagocyte NADPH oxidase, oxidative stress and lipids: anti- or pro ageing? Mech Ageing Dev 172:30–34CrossRefPubMedGoogle Scholar
  95. 95.
    Sohal RS, Orr WC (2012) The redox stress hypothesis of aging. Free Radic Biol Med 52(3):539–555CrossRefPubMedGoogle Scholar
  96. 96.
    Go YM, Jones DP (1979) Redox theory of aging: implications for health and disease. Clin Sci (Lond) 131(14):1669–1688CrossRefGoogle Scholar
  97. 97.
    Barja G (2002) Rate of generation of oxidative stress-related damage and animal longevity. Free Radic Biol Med 33(9):1167–1172CrossRefPubMedGoogle Scholar
  98. 98.
    Schindeldecker M, Stark M, Behl C, Moosmann B (2011) Differential cysteine depletion in respiratory chain complexes enables the distinction of longevity from aerobicity. Mech Ageing Dev 132(4):171–179CrossRefPubMedGoogle Scholar
  99. 99.
    Paradies G, Paradies V, Ruggiero FM, Petrosillo G (2014) Cardiolipin and mitochondrial function in health and disease. Antioxid Redox Signal 20(12):1925–1953CrossRefPubMedGoogle Scholar
  100. 100.
    Pollak N, Dölle C, Ziegler M (2007) The power to reduce: pyridine nucleotides--small molecules with a multitude of functions. Biochem J 402(2):205–218CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Copes N, Edwards C, Chaput D, Saifee M, Barjuca I, Nelson D et al (2015) Metabolome and proteome changes with aging in Caenorhabditis elegans. Exp Gerontol 72:67–84CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Mouchiroud L, Houtkooper RH, Moullan N, Katsyuba E, Ryu D, Cantó C et al (2013) The NAD(+)/Sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell 154(2):430–441CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Gomes AP, Price NL, Ling AJ, Moslehi JJ, Montgomery MK, Rajman L et al (2013) Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 155(7):1624–1638CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Ren X, Zou L, Zhang X, Branco V, Wang J, Carvalho C et al (2017) Redox signaling mediated by thioredoxin and glutathione systems in the central nervous system. Antioxid Redox Signal 27(13):989–1010CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Veech RL, Bradshaw PC, Clarke K, Curtis W, Pawlosky R, King MT (2017) Ketone bodies mimic the life span extending properties of caloric restriction. IUBMB Life 69(5):305–314CrossRefPubMedGoogle Scholar
  106. 106.
    Veech RL, Eggleston LV, Krebs HA (1969) The redox state of free nicotinamide-adenine dinucleotide phosphate in the cytoplasm of rat liver. Biochem J 115(4):609–619CrossRefPubMedPubMedCentralGoogle Scholar
  107. 107.
    Tischler ME, Friedrichs D, Coll K, Williamson JR (1977) Pyridine nucleotide distributions and enzyme mass action ratios in hepatocytes from fed and starved rats. Arch Biochem Biophys 184(1):222–236CrossRefPubMedGoogle Scholar
  108. 108.
    Hanson GT, Aggeler R, Oglesbee D, Cannon M, Capaldi RA, Tsien RY et al (2004) Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators. J Biol Chem 279(13):13044–13053CrossRefPubMedGoogle Scholar
  109. 109.
    Bradshaw PC (2019) Cytoplasmic and mitochondrial NADPH-coupled redox systems in the regulation of aging. Nutrients 11(3). pii: E504.  https://doi.org/10.3390/nu11030504CrossRefPubMedCentralGoogle Scholar
  110. 110.
    Inoue K, Zhuang L, Ganapathy V (2002) Human Na+ -coupled citrate transporter: primary structure, genomic organization, and transport function. Biochem Biophys Res Commun 299(3):465–471CrossRefPubMedGoogle Scholar
  111. 111.
    Rogina B, Reenan RA, Nilsen SP, Helfand SL (2000) Extended life-span conferred by cotransporter gene mutations in Drosophila. Science 290(5499):2137–2140CrossRefPubMedGoogle Scholar
  112. 112.
    Anderson RM, Weindruch R (2012) The caloric restriction paradigm: implications for healthy human aging. Am J Hum Biol 24(2):101–106CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Birkenfeld AL, Lee HY, Guebre-Egziabher F, Alves TC, Jurczak MJ, Jornayvaz FR et al (2011) Deletion of the mammalian INDY homolog mimics aspects of dietary restriction and protects against adiposity and insulin resistance in mice. Cell Metab 14(2):184–195CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Gregolin C, Ryder E, Kleinschmidt AK, Warner RC, Lane MD (1966) Molecular characteristics of liver acetyl CoA carboxylase. Proc Natl Acad Sci U S A 56(1):148–155CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Fu JY, Kemp RG (1973) Activation of muscle fructose 1,6-diphosphatase by creatine phosphate and citrate. J Biol Chem 248(3):1124–1125PubMedGoogle Scholar
  116. 116.
    Nielsen TT (1983) Plasma citrate in relation to glucose and free fatty acid metabolism in man. Dan Med Bull 30(6):357–378PubMedGoogle Scholar
  117. 117.
    Ros S, Schulze A (2013) Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism. Cancer Metab 1(1):8.  https://doi.org/10.1186/2049-3002-1-8CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Huard K, Brown J, Jones JC, Cabral S, Futatsugi K, Gorgoglione M et al (2015) Discovery and characterization of novel inhibitors of the sodium-coupled citrate transporter (NaCT or SLC13A5). Sci Rep 5:17391.  https://doi.org/10.1038/srep17391CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Wang PY, Neretti N, Whitaker R, Hosier S, Chang C, Lu D et al (2009) Long-lived Indy and calorie restriction interact to extend life span. Proc Natl Acad Sci U S A 106(23):9262–9267CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Pijpe J, Pul N, van Duijn S, Brakefield PM, Zwaan BJ (2011) Changed gene expression for candidate ageing genes in long-lived Bicyclus anynana butterflies. Exp Gerontol 46(6):426–434CrossRefPubMedGoogle Scholar
  121. 121.
    Martinez-Beamonte R, Navarro MA, Guillen N, Acin S, Arnal C, Guzman MA et al (2011) Postprandial transcriptome associated with virgin olive oil intake in rat liver. Front Biosci (Elite Ed) 3:11–21Google Scholar
  122. 122.
    Etcheverry A, Aubry M, de Tayrac M, Vauleon E, Boniface R, Guenot F et al (2010) DNA methylation in glioblastoma: impact on gene expression and clinical outcome. BMC Genomics 11:701.  https://doi.org/10.1186/1471-2164-11-701CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Tian Y, Arai E, Gotoh M, Komiyama M, Fujimoto H, Kanai Y (2014) Prognostication of patients with clear cell renal cell carcinomas based on quantification of DNA methylation levels of CpG island methylator phenotype marker genes. BMC Cancer 14:772.  https://doi.org/10.1186/1471-2407-14-772CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Díaz M, García C, Sebastiani G, de Zegher F, López-Bermejo A, Ibáñez L (2016) Placental and cord blood methylation of genes involved in energy homeostasis: association with fetal growth and neonatal body composition. Diabetes 66(3):779–784.  https://doi.org/10.2337/db16-0776CrossRefPubMedGoogle Scholar
  125. 125.
    Neretti N, Wang PY, Brodsky AS, Nyguyen HH, White KP, Rogina B et al (2009) Long-lived Indy induces reduced mitochondrial reactive oxygen species production and oxidative damage. Proc Natl Acad Sci U S A 106(7):2277–2282CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Neuschäfer-Rube F, Lieske S, Kuna M, Henkel J, Perry RJ, Erion DM, Pesta D et al (2014) The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes. Diabetes 63(3):1048–1057CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    von Loeffelholz C, Döcke S, Lock JF, Lieske S, Horn P, Kriebel J et al (2017) Increased lipogenesis in spite of upregulated hepatic 5’AMP-activated protein kinase in human non-alcoholic fatty liver. Hepatol Res 47(9):890–901CrossRefGoogle Scholar
  128. 128.
    Willmes DM, Helfand SL, Birkenfeld AL (2016) The longevity transporter mIndy (Slc13a5) as a target for treating hepatic steatosis and insulin resistance. Aging (Albany NY) 8(2):208–209CrossRefGoogle Scholar
  129. 129.
    Willmes DM, Kurzbach A, Henke C, Schumann T, Zahn G, Heifetz A et al (2018) The longevity gene INDY (I’m Not Dead Yet) in metabolic control: potential as pharmacological target. Pharmacol Ther 185:1–11CrossRefPubMedGoogle Scholar
  130. 130.
    Brachs S, Winkel AF, Tang H, Birkenfeld AL, Brunner B, Jahn-Hofmann K et al (2016) Inhibition of citrate cotransporter Slc13a5/mINDY by RNAi improves hepatic insulin sensitivity and prevents diet-induced non-alcoholic fatty liver disease in mice. Mol Metab 5(11):1072–1082CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Guest PC (ed) (2019) Reviews on biomarker studies of metabolic and metabolism-related disorders. In: Advances in experimental medicine and biology, 1st edn. Springer, Cham. ISBN-10: 3030126676Google Scholar
  132. 132.
  133. 133.
    Flegal KM, Kit BK, Orpana H, Graubard BI (2013) Association of all-cause mortality with overweight and obesity using standard body mass index categories a systematic review and meta-analysis. JAMA 309(1):71–82CrossRefPubMedPubMedCentralGoogle Scholar
  134. 134.
    Aune D, Sen A, Prasad M, Norat T, Janszky I, Tonstad S et al (2016) BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ 353:i2156.  https://doi.org/10.1136/bmj.i2156CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Di Angelantonio E, Bhupathiraju SN, Wormser D, Gao P, Kaptoge S, de Gonzalez AB et al (2016) Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 388(10046):776–786CrossRefPubMedGoogle Scholar
  136. 136.
    Hubert HB, Feinleib M, McNamara PM, Castelli WP (1983) Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 67(5):968–977CrossRefPubMedGoogle Scholar
  137. 137.
    Sacco MR, de Castro NP, Euclydes VLV, Souza JM, Rondó PH (2013) Birth weight, rapid weight gain in infancy and markers of overweight and obesity in childhood. Eur J Clin Nutr 67(11):1147–1153CrossRefPubMedGoogle Scholar
  138. 138.
    Heitmann BL, Lissner L (1995) Dietary underreporting by obese individuals--is it specific or non-specific? BMJ 311(7011):986–989CrossRefPubMedPubMedCentralGoogle Scholar
  139. 139.
    Hariri N, Thibault L (2010) High-fat diet-induced obesity in animal models. Nutr Res Rev 23(2):270–299CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Ong TP, Guest PC (2018) Nutritional programming effects on development of metabolic disorders in later life. Methods Mol Biol 1735:3–17CrossRefPubMedGoogle Scholar
  141. 141.
    Mickelsen O, Takahashi S, Craig C (1955) Experimental obesity. J Nutr 57:541–554CrossRefPubMedGoogle Scholar
  142. 142.
    Buettner R, Schölmerich J, Bollheimer LC (2007) High-fat diets: modeling the metabolic disorders of human obesity in rodents. Obesity (Silver Spring) 15(4):798–808CrossRefGoogle Scholar
  143. 143.
    Woods SC, D’Alessio DA, Tso P, Rushing PA, Clegg DJ, Benoit SC et al (2004) Consumption of a high-fat diet alters the homeostatic regulation of energy balance. Physiol Behav 83(4):573–578CrossRefPubMedGoogle Scholar
  144. 144.
    Fontelles CC, Guido LN, Rosim MP et al (2016) Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets. Breast Cancer Res 18:71.  https://doi.org/10.1186/s13058-016-0729-xCrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Hariri N, Gougeon R, Thibault L (2010) A highly saturated fat-rich diet is more obesogenic than diets with lower saturated fat content. Nutr Res 30(9):632–643CrossRefPubMedGoogle Scholar
  146. 146.
    Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF et al (2000) Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 105(8):1049–1056CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Pinheiro-Castro N, Silva LBAR, Novaes GM, Ong TP (2019) Hypercaloric diet-induced obesity and obesity-related metabolic disorders in experimental models. Adv Exp Med Biol 1134:149–161CrossRefPubMedGoogle Scholar
  148. 148.
    Berridge KC, Ho C-Y, Richard JM, DiFeliceantonio AG (2010) The tempted brain eats: pleasure and desire circuits in obesity and eating disorders. Brain Res 1350:43–64CrossRefPubMedPubMedCentralGoogle Scholar
  149. 149.
    Castro L, Gao X, Moore AB, Yu L, Di X, Kissling GE et al (2016) A high concentration of genistein induces cell death in human uterine leiomyoma cells by autophagy. Expert Opin Environ Biol 5(Suppl 1).  https://doi.org/10.4172/2325-9655.S1-003
  150. 150.
    Sampey BP, Vanhoose AM, Winfield HM, Freemerman AJ, Muehlbauer MJ, Fueger PT et al (2011) Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity 19(6):1109–1117CrossRefPubMedGoogle Scholar
  151. 151.
    Zeeni N, Dagher-Hamalian C, Dimassi H, Faour WH (2015) Cafeteria diet-fed mice is a pertinent model of obesity-induced organ damage: a potential role of inflammation. Inflamm Res 64(7):501–512CrossRefPubMedGoogle Scholar
  152. 152.
    Maioli TU, Gonçalves JL, Miranda MCG, Martins VD, Horta LS, Moreira TG et al (2016) High sugar and butter (HSB) diet induces obesity and metabolic syndrome with decrease in regulatory T cells in adipose tissue of mice. Inflamm Res 65(2):169–178CrossRefPubMedGoogle Scholar
  153. 153.
    Crescenzo R, Bianco F, Mazzoli A, Giacco A, Cancelliere R, di Fabio GA et al (2015) Fat quality influences the obesogenic effect of high fat diets. Nutrients 7(11):9475–9491CrossRefPubMedPubMedCentralGoogle Scholar
  154. 154.
    Aller EEJG, Abete I, Astrup A, Martinez JA, van Baak MA (2011) Starches, sugars and obesity. Nutrients 3(3):341–369CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Lennerz B, Lennerz JK (2018) Food addiction, high-glycemic-index carbohydrates, and obesity. Clin Chem 64(1):64–71CrossRefPubMedGoogle Scholar
  156. 156.
    Panchal SK, Poudyal H, Iyer A, Nazer R, Alam MA, Diwan V et al (2011) High-carbohydrate, high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats. J Cardiovasc Pharmacol 57(5):611–624CrossRefPubMedGoogle Scholar
  157. 157.
    Hung WW, Ross JS, Boockvar KS, Siu AL (2011) Recent trends in chronic disease, impairment and disability among older adults in the United States. BMC Geriatr 11:47.  https://doi.org/10.1186/1471-2318-11-47CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Madreiter-Sokolowski CT, Sokolowski AA, Waldeck-Weiermair M, Malli R, Graier WF (2018) Targeting mitochondria to counteract age-related cellular dysfunction. Genes (Basel) 9(3):pii: E165.  https://doi.org/10.3390/genes9030165CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Paul C. Guest
    • 1
  1. 1.Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of BiologyUniversity of Campinas (UNICAMP)CampinasBrazil

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