Advertisement

Biogerontology

, Volume 19, Issue 6, pp 461–480 | Cite as

Mitochondrial dysfunction in metabolism and ageing: shared mechanisms and outcomes?

  • Guillermo López-Lluch
  • Juan Diego Hernández-Camacho
  • Daniel J. Moreno Fernández-Ayala
  • Plácido Navas
Review Article

Abstract

Mitochondria are key in the metabolism of aerobic organisms and in ageing progression and age-related diseases. Mitochondria are essential for obtaining ATP from glucose and fatty acids but also in many other essential functions in cells including aminoacids metabolism, pyridine synthesis, phospholipid modifications and calcium regulation. On the other hand, the activity of mitochondria is also the principal source of reactive oxygen species in cells. Ageing and chronic age-related diseases are associated with the deregulation of cell metabolism and dysfunction of mitochondria. Cell metabolism is controlled by three major nutritional sensors: mTOR, AMPK and Sirtuins. These factors control mitochondrial biogenesis and dynamics by regulating fusion, fission and turnover through mito- and autophagy. A complex interaction between the activity of these nutritional sensors, mitochondrial biogenesis rate and dynamics exists and affect ageing, age-related diseases including metabolic disease. Further, mitochondria maintain a constant communication with nucleus modulating gene expression and modifying epigenetics. In this review we highlight the importance of mitochondria in ageing and the repercussion in the progression of age-related diseases and metabolic disease.

Keywords

Mitochondria Metabolism Ageing Metabolic syndrome Fat Mitochondrial dynamics ROS 

Notes

Funding

The research group is funded by the Andalusian Government Grant BIO177 (FEDER funds of European Commission). Research has been funded by the Spanish Ministry of Economy and Competitiveness Grant DEP2012-39985 and Instituto de Salud Carlos III FIS Grant PI14/01962. Authors are also members of the CIBERER, Instituto Carlos III, of the Spanish Ministry of Health.

References

  1. Aagaard-Tillery KM, Grove K, Bishop J, Ke X, Fu Q, McKnight R, Lane RH (2008) Developmental origins of disease and determinants of chromatin structure: maternal diet modifies the primate fetal epigenome. J Mol Endocrinol 41(2):91–102.  https://doi.org/10.1677/JME-08-0025 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr, International Diabetes Federation Task Force on E, Prevention, Hational Heart L, Blood I, American Heart A, World Heart F, International Atherosclerosis S, International Association for the Study of O (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120(16):1640–1645.  https://doi.org/10.1161/circulationaha.109.192644 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Alers S, Loffler AS, Wesselborg S, Stork B (2012) Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 32(1):2–11.  https://doi.org/10.1128/MCB.06159-11 CrossRefPubMedPubMedCentralGoogle Scholar
  4. Artal-Sanz M, Tavernarakis N (2009) Prohibitin couples diapause signalling to mitochondrial metabolism during ageing in C. elegans. Nature 461(7265):793–797.  https://doi.org/10.1038/nature08466 CrossRefPubMedGoogle Scholar
  5. Bach D, Pich S, Soriano FX, Vega N, Baumgartner B, Oriola J, Daugaard JR, Lloberas J, Camps M, Zierath JR, Rabasa-Lhoret R, Wallberg-Henriksson H, Laville M, Palacin M, Vidal H, Rivera F, Brand M, Zorzano A (2003) Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem 278(19):17190–17197.  https://doi.org/10.1074/jbc.M212754200 CrossRefPubMedGoogle Scholar
  6. Bach D, Naon D, Pich S, Soriano FX, Vega N, Rieusset J, Laville M, Guillet C, Boirie Y, Wallberg-Henriksson H, Manco M, Calvani M, Castagneto M, Palacin M, Mingrone G, Zierath JR, Vidal H, Zorzano A (2005) Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6. Diabetes 54(9):2685–2693CrossRefGoogle Scholar
  7. Bae SH, Sung SH, Oh SY, Lim JM, Lee SK, Park YN, Lee HE, Kang D, Rhee SG (2013) Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab 17(1):73–84.  https://doi.org/10.1016/j.cmet.2012.12.002 CrossRefPubMedGoogle Scholar
  8. Barbieri E, Sestili P, Vallorani L, Guescini M, Calcabrini C, Gioacchini AM, Annibalini G, Lucertini F, Piccoli G, Stocchi V (2013) Mitohormesis in muscle cells: a morphological, molecular, and proteomic approach. Muscles Ligaments Tendons J 3(4):254–266PubMedGoogle Scholar
  9. Battino M, Gorini A, Villa RF, Genova ML, Bovina C, Sassi S, Littarru GP, Lenaz G (1995) Coenzyme Q content in synaptic and non-synaptic mitochondria from different brain regions in the ageing rat. Mech Ageing Dev 78(3):173–187CrossRefGoogle Scholar
  10. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444(7117):337–342.  https://doi.org/10.1038/nature05354 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Baur JA, Chen D, Chini EN, Chua K, Cohen HY, de Cabo R, Deng C, Dimmeler S, Gius D, Guarente LP, Helfand SL, Imai S, Itoh H, Kadowaki T, Koya D, Leeuwenburgh C, McBurney M, Nabeshima Y, Neri C, Oberdoerffer P, Pestell RG, Rogina B, Sadoshima J, Sartorelli V, Serrano M, Sinclair DA, Steegborn C, Tatar M, Tissenbaum HA, Tong Q, Tsubota K, Vaquero A, Verdin E (2010) Dietary restriction: standing up for sirtuins. Science 329(5995):1012–1013.  https://doi.org/10.1126/science.329.5995.1012 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bennett CF, Vander Wende H, Simko M, Klum S, Barfield S, Choi H, Pineda VV, Kaeberlein M (2014) Activation of the mitochondrial unfolded protein response does not predict longevity in Caenorhabditis elegans. Nat Commun 5:3483.  https://doi.org/10.1038/ncomms4483 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Beregi E, Regius O (1987) Comparative morphological study of age related mitochondrial changes of the lymphocytes and skeletal muscle cells. Acta Morphol Hung 35(3–4):219–224PubMedGoogle Scholar
  14. Beyer RE, Burnett BA, Cartwright KJ, Edington DW, Falzon MJ, Kreitman KR, Kuhn TW, Ramp BJ, Rhee SY, Rosenwasser MJ et al (1985) Tissue coenzyme Q (ubiquinone) and protein concentrations over the life span of the laboratory rat. Mech Ageing Dev 32(2–3):267–281CrossRefGoogle Scholar
  15. Biel TG, Lee S, Flores-Toro JA, Dean JW, Go KL, Lee MH, Law BK, Law ME, Dunn WA Jr, Zendejas I, Behrns KE, Kim JS (2016) Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner. Cell Death Differ 23(2):279–290.  https://doi.org/10.1038/cdd.2015.96 CrossRefPubMedGoogle Scholar
  16. Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299(5606):572–574.  https://doi.org/10.1126/science.1078223 CrossRefPubMedGoogle Scholar
  17. Boengler K, Kosiol M, Mayr M, Schulz R, Rohrbach S (2017) Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle 8(3):349–369.  https://doi.org/10.1002/jcsm.12178 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Borengasser SJ, Kang P, Faske J, Gomez-Acevedo H, Blackburn ML, Badger TM, Shankar K (2014) High fat diet and in utero exposure to maternal obesity disrupts circadian rhythm and leads to metabolic programming of liver in rat offspring. PLoS ONE 9(1):e84209.  https://doi.org/10.1371/journal.pone.0084209 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Bratic I, Trifunovic A (2010) Mitochondrial energy metabolism and ageing. Biochim Biophys Acta 1797(6–7):961–967.  https://doi.org/10.1016/j.bbabio.2010.01.004 CrossRefPubMedGoogle Scholar
  20. Budanov AV, Karin M (2008) p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 134(3):451–460.  https://doi.org/10.1016/j.cell.2008.06.028 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Burkewitz K, Zhang Y, Mair WB (2014) AMPK at the nexus of energetics and aging. Cell Metab 20(1):10–25.  https://doi.org/10.1016/j.cmet.2014.03.002 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Canto C, Jiang LQ, Deshmukh AS, Mataki C, Coste A, Lagouge M, Zierath JR, Auwerx J (2010) Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 11(3):213–219.  https://doi.org/10.1016/j.cmet.2010.02.006 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Cartoni R, Leger B, Hock MB, Praz M, Crettenand A, Pich S, Ziltener JL, Luthi F, Deriaz O, Zorzano A, Gobelet C, Kralli A, Russell AP (2005) Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle after physical exercise. J Physiol 567(Pt 1):349–358.  https://doi.org/10.1113/jphysiol.2005.092031 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Cela O, Scrima R, Pazienza V, Merla G, Benegiamo G, Augello B, Fugetto S, Menga M, Rubino R, Fuhr L, Relogio A, Piccoli C, Mazzoccoli G, Capitanio N (2016) Clock genes-dependent acetylation of complex I sets rhythmic activity of mitochondrial OxPhos. Biochim Biophys Acta 4:596–606.  https://doi.org/10.1016/j.bbamcr.2015.12.018 CrossRefGoogle Scholar
  25. Chan EY (2009) mTORC1 phosphorylates the ULK1-mAtg13-FIP200 autophagy regulatory complex. Sci Signal 2(84):pe51.  https://doi.org/10.1126/scisignal.284pe51 CrossRefPubMedGoogle Scholar
  26. Chen H, Chan DC (2005) Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14(2):R283–289.  https://doi.org/10.1093/hmg/ddi270 CrossRefPubMedGoogle Scholar
  27. Chen G, Liang G, Ou J, Goldstein JL, Brown MS (2004) Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver. Proc Natl Acad Sci USA 101(31):11245–11250.  https://doi.org/10.1073/pnas.0404297101 CrossRefPubMedGoogle Scholar
  28. Chen L, Liu J, Tao X, Wang G, Wang Q, Liu X (2015) The role of Pin1 protein in aging of human tendon stem/progenitor cells. Biochem Biophys Res Commun 464(2):487–492.  https://doi.org/10.1016/j.bbrc.2015.06.163 CrossRefPubMedGoogle Scholar
  29. Chistiakov DA, Sobenin IA, Revin VV, Orekhov AN, Bobryshev YV (2014) Mitochondrial aging and age-related dysfunction of mitochondria. Biomed Res Int 2014:238463.  https://doi.org/10.1155/2014/238463 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Choi KM, Lee HL, Kwon YY, Kang MS, Lee SK, Lee CK (2013) Enhancement of mitochondrial function correlates with the extension of lifespan by caloric restriction and caloric restriction mimetics in yeast. Biochem Biophys Res Commun 441(1):236–242.  https://doi.org/10.1016/j.bbrc.2013.10.049 CrossRefPubMedGoogle Scholar
  31. Ciccarone F, Tagliatesta S, Caiafa P, Zampieri M (2017) DNA methylation dynamics in aging: how far are we from understanding the mechanisms? Mech Ageing Dev.  https://doi.org/10.1016/j.mad.2017.12.002 CrossRefPubMedGoogle Scholar
  32. Clark AT (2015) DNA methylation remodeling in vitro and in vivo. Curr Opin Genet Dev 34:82–87.  https://doi.org/10.1016/j.gde.2015.09.002 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305(5682):390–392.  https://doi.org/10.1126/science.1099196 CrossRefGoogle Scholar
  34. Conley KE, Jubrias SA, Esselman PC (2000) Oxidative capacity and ageing in human muscle. J Physiol 526(Pt 1):203–210CrossRefGoogle Scholar
  35. Cowey S, Hardy RW (2006) The metabolic syndrome: a high-risk state for cancer? Am J Pathol 169(5):1505–1522.  https://doi.org/10.2353/ajpath.2006.051090 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Das SK, Balasubramanian P, Weerasekara YK (2017) Nutrition modulation of human aging: the calorie restriction paradigm. Mol Cell Endocrinol 455:148–157.  https://doi.org/10.1016/j.mce.2017.04.011 CrossRefPubMedGoogle Scholar
  37. de Brito OM, Scorrano L (2008) Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456(7222):605–610.  https://doi.org/10.1038/nature07534 CrossRefPubMedGoogle Scholar
  38. de Brito OM, Scorrano L (2009) Mitofusin-2 regulates mitochondrial and endoplasmic reticulum morphology and tethering: the role of Ras. Mitochondrion 9(3):222–226.  https://doi.org/10.1016/j.mito.2009.02.005 CrossRefPubMedGoogle Scholar
  39. de Cabo R, Carmona-Gutierrez D, Bernier M, Hall MN, Madeo F (2014) The search for antiaging interventions: from elixirs to fasting regimens. Cell 157(7):1515–1526.  https://doi.org/10.1016/j.cell.2014.05.031 CrossRefPubMedPubMedCentralGoogle Scholar
  40. de Goede P, Wefers J, Brombacher EC, Schrauwen P, Kalsbeek A (2018) Circadian rhythms in mitochondrial respiration. J Mol Endocrinol 60(3):R115–R130.  https://doi.org/10.1530/JME-17-0196 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Del Pozo-Cruz J, Rodriguez-Bies E, Navas-Enamorado I, Del Pozo-Cruz B, Navas P, Lopez-Lluch G (2014) Relationship between functional capacity and body mass index with plasma coenzyme Q10 and oxidative damage in community-dwelling elderly-people. Exp Gerontol 52:46–54.  https://doi.org/10.1016/j.exger.2014.01.026 CrossRefPubMedGoogle Scholar
  42. Dencher NA, Frenzel M, Reifschneider NH, Sugawa M, Krause F (2007) Proteome alterations in rat mitochondria caused by aging. Ann N Y Acad Sci 1100:291–298.  https://doi.org/10.1196/annals.1395.030 CrossRefPubMedGoogle Scholar
  43. Denzer I, Munch G, Friedland K (2016) Modulation of mitochondrial dysfunction in neurodegenerative diseases via activation of nuclear factor erythroid-2-related factor 2 by food-derived compounds. Pharmacol Res 103:80–94.  https://doi.org/10.1016/j.phrs.2015.11.019 CrossRefPubMedGoogle Scholar
  44. Dolinsky VW, Rogan KJ, Sung MM, Zordoky BN, Haykowsky MJ, Young ME, Jones LW, Dyck JR (2013) Both aerobic exercise and resveratrol supplementation attenuate doxorubicin-induced cardiac injury in mice. Am J Physiol Endocrinol Metab 305(2):E243–253.  https://doi.org/10.1152/ajpendo.00044.2013 CrossRefPubMedPubMedCentralGoogle Scholar
  45. Elmquist JK, Coppari R, Balthasar N, Ichinose M, Lowell BB (2005) Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J Comp Neurol 493(1):63–71.  https://doi.org/10.1002/cne.20786 CrossRefPubMedGoogle Scholar
  46. Fabbri E, Chia CW, Spencer RG, Fishbein KW, Reiter DA, Cameron D, Zane AC, Moore ZA, Gonzalez-Freire M, Zoli M, Studenski SA, Kalyani RR, Egan JM, Ferrucci L (2017) Insulin resistance is associated with reduced mitochondrial oxidative capacity measured by 31P-magnetic resonance spectroscopy in participants without diabetes from the baltimore longitudinal study of aging. Diabetes 66(1):170–176.  https://doi.org/10.2337/db16-0754 CrossRefPubMedGoogle Scholar
  47. Fang EF, Waltz TB, Kassahun H, Lu Q, Kerr JS, Morevati M, Fivenson EM, Wollman BN, Marosi K, Iser WB, Eckley DM, Zhang Y, Lehrmann E, Goldberg IG, Scheibye-Knudsen M, Mattson MP, Nilsen H, Bohr VA, Becker KG (2017) Tomatidine enhances lifespan and healthspan in C. elegans through mitophagy induction via the SKN-1/Nrf2 pathway. Sci Rep 7:46208.  https://doi.org/10.1038/srep46208 CrossRefPubMedPubMedCentralGoogle Scholar
  48. Feige JN, Lagouge M, Auwerx J (2008) Dietary manipulation of mouse metabolism. Curr Protoc Mol Biol 84(1):29B-5.  https://doi.org/10.1002/0471142727.mb29b05s84 CrossRefGoogle Scholar
  49. Feil R, Fraga MF (2012) Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet 13(2):97–109.  https://doi.org/10.1038/nrg3142 CrossRefPubMedGoogle Scholar
  50. Feng S, Jacobsen SE, Reik W (2010) Epigenetic reprogramming in plant and animal development. Science 330(6004):622–627.  https://doi.org/10.1126/science.1190614 CrossRefPubMedPubMedCentralGoogle Scholar
  51. Fernandez-Ayala DJ, Chen S, Kemppainen E, O’Dell KM, Jacobs HT (2010) Gene expression in a Drosophila model of mitochondrial disease. PLoS ONE 5(1):e8549.  https://doi.org/10.1371/journal.pone.0008549 CrossRefPubMedPubMedCentralGoogle Scholar
  52. Fernandez-Ayala DJ, Guerra I, Jimenez-Gancedo S, Cascajo MV, Gavilan A, Dimauro S, Hirano M, Briones P, Artuch R, De Cabo R, Salviati L, Navas P (2013) Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies. BMJ Open 3(3):e002524.  https://doi.org/10.1136/bmjopen-2012-002524 CrossRefPubMedPubMedCentralGoogle Scholar
  53. Fraga MF, Ballestar E, Paz MF, Ropero S, Setien F, Ballestar ML, Heine-Suner D, Cigudosa JC, Urioste M, Benitez J, Boix-Chornet M, Sanchez-Aguilera A, Ling C, Carlsson E, Poulsen P, Vaag A, Stephan Z, Spector TD, Wu YZ, Plass C, Esteller M (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102(30):10604–10609.  https://doi.org/10.1073/pnas.0500398102 CrossRefPubMedGoogle Scholar
  54. Garatachea N, Pareja-Galeano H, Sanchis-Gomar F, Santos-Lozano A, Fiuza-Luces C, Moran M, Emanuele E, Joyner MJ, Lucia A (2015) Exercise attenuates the major hallmarks of aging. Rejuvenation Res 18(1):57–89.  https://doi.org/10.1089/rej.2014.1623 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Genova ML, Lenaz G (2015) The interplay between respiratory supercomplexes and ROS in aging. Antioxid Redox Signal 23:208–238.  https://doi.org/10.1089/ars.2014.6214 CrossRefPubMedGoogle Scholar
  56. Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J 26(7):1913–1923.  https://doi.org/10.1038/sj.emboj.7601633 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Gomes LC, Scorrano L (2008) High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim Biophys Acta 1777(7–8):860–866.  https://doi.org/10.1016/j.bbabio.2008.05.442 CrossRefPubMedGoogle Scholar
  58. Gomes LC, Scorrano L (2011) Mitochondrial elongation during autophagy: a stereotypical response to survive in difficult times. Autophagy 7(10):1251–1253.  https://doi.org/10.4161/auto.7.10.16771 CrossRefPubMedPubMedCentralGoogle Scholar
  59. Gomez LA, Hagen TM (2012) Age-related decline in mitochondrial bioenergetics: does supercomplex destabilization determine lower oxidative capacity and higher superoxide production? Semin Cell Dev Biol 23(7):758–767.  https://doi.org/10.1016/j.semcdb.2012.04.002 CrossRefPubMedGoogle Scholar
  60. Goncalves RL, Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, Brand MD (2015) Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise. J Biol Chem 290(1):209–227.  https://doi.org/10.1074/jbc.M114.619072 CrossRefPubMedGoogle Scholar
  61. Gong C, Li C, Qi X, Song Z, Wu J, Hughes ME, Li X (2015) The daily rhythms of mitochondrial gene expression and oxidative stress regulation are altered by aging in the mouse liver. Chronobiol Int 32(9):1254–1263.  https://doi.org/10.3109/07420528.2015.1085388 CrossRefPubMedGoogle Scholar
  62. Gonzalez-Freire M, Cabo Rd, Bernier M, Sollott SJ, Fabbri E, Navas P, Ferrucci L (2015) Reconsidering the role of mitochondria in aging. J Gerontol Ser A.  https://doi.org/10.1093/gerona/glv070 CrossRefGoogle Scholar
  63. Goto T, Takano M (2009) Transcriptional role of FOXO1 in drug resistance through antioxidant defense systems. Adv Exp Med Biol 665:171–179CrossRefGoogle Scholar
  64. Gouspillou G, Sgarioto N, Norris B, Barbat-Artigas S, Aubertin-Leheudre M, Morais JA, Burelle Y, Taivassalo T, Hepple RT (2014) The relationship between muscle fiber type-specific PGC-1alpha content and mitochondrial content varies between rodent models and humans. PLoS ONE 9(8):e103044.  https://doi.org/10.1371/journal.pone.0103044 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Grazioli E, Dimauro I, Mercatelli N, Wang G, Pitsiladis Y, Di Luigi L, Caporossi D (2017) Physical activity in the prevention of human diseases: role of epigenetic modifications. BMC Genomics 18(Suppl 8):802.  https://doi.org/10.1186/s12864-017-4193-5 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Grefhorst A, Elzinga BM, Voshol PJ, Plosch T, Kok T, Bloks VW, van der Sluijs FH, Havekes LM, Romijn JA, Verkade HJ, Kuipers F (2002) Stimulation of lipogenesis by pharmacological activation of the liver X receptor leads to production of large, triglyceride-rich very low density lipoprotein particles. J Biol Chem 277(37):34182–34190.  https://doi.org/10.1074/jbc.M204887200 CrossRefPubMedGoogle Scholar
  67. Griffin TM, Humphries KM, Kinter M, Lim HY, Szweda LI (2015) Nutrient sensing and utilization: getting to the heart of metabolic flexibility. Biochimie.  https://doi.org/10.1016/j.biochi.2015.10.013 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Guaras A, Perales-Clemente E, Calvo E, Acin-Perez R, Loureiro-Lopez M, Pujol C, Martinez-Carrascoso I, Nunez E, Garcia-Marques F, Rodriguez-Hernandez MA, Cortes A, Diaz F, Perez-Martos A, Moraes CT, Fernandez-Silva P, Trifunovic A, Navas P, Vazquez J, Enriquez JA (2016) The CoQH2/CoQ ratio serves as a sensor of respiratory chain efficiency. Cell Rep 15(1):197–209.  https://doi.org/10.1016/j.celrep.2016.03.009 CrossRefPubMedGoogle Scholar
  69. Guarente L (2011) Sirtuins, aging, and metabolism. Cold Spring Harb Symp Quant Biol 76:81–90.  https://doi.org/10.1101/sqb.2011.76.010629 CrossRefPubMedGoogle Scholar
  70. Guarente L (2013) Calorie restriction and sirtuins revisited. Genes Dev 27(19):2072–2085.  https://doi.org/10.1101/gad.227439.113 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Gvozdjakova A, Kucharska J, Tkacov M, Singh RB, Hlavata A (2012) Ratio of lipid parameters to coenzyme Q10 could be used as biomarker of the development of early complications of obesity in children. Bratisl Lek Listy 113(1):21–25PubMedGoogle Scholar
  72. Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30(2):214–226.  https://doi.org/10.1016/j.molcel.2008.03.003 CrossRefPubMedPubMedCentralGoogle Scholar
  73. Hafizi Abu Bakar M, Kian Kai C, Wan Hassan WN, Sarmidi MR, Yaakob H, Zaman Huri H (2015) Mitochondrial dysfunction as a central event for mechanisms underlying insulin resistance: the roles of long chain fatty acids. Diabetes Metab Res Rev 31(5):453–475.  https://doi.org/10.1002/dmrr.2601 CrossRefPubMedGoogle Scholar
  74. Halling JF, Pilegaard H (2017) Autophagy-dependent beneficial effects of exercise. Cold Spring Harb Perspect Med 7(8):a029777.  https://doi.org/10.1101/cshperspect.a029777 CrossRefPubMedGoogle Scholar
  75. Halling JF, Ringholm S, Olesen J, Prats C, Pilegaard H (2017) Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1alpha dependent manner. Exp Gerontol 96:1–6.  https://doi.org/10.1016/j.exger.2017.05.020 CrossRefPubMedGoogle Scholar
  76. Handschin C, Spiegelman BM (2006) Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. Endocr Rev 27(7):728–735.  https://doi.org/10.1210/er.2006-0037 CrossRefPubMedGoogle Scholar
  77. Hardie DG (2011) Sensing of energy and nutrients by AMP-activated protein kinase. Am J Clin Nutr 93(4):891S–896.  https://doi.org/10.3945/ajcn.110.001925 CrossRefPubMedGoogle Scholar
  78. Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13(4):251–262.  https://doi.org/10.1038/nrm3311 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300CrossRefGoogle Scholar
  80. Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20(4):145–147CrossRefGoogle Scholar
  81. Harper JW, Ordureau A, Heo JM (2018) Building and decoding ubiquitin chains for mitophagy. Nat Rev Mol Cell Biol 19(2):93–108.  https://doi.org/10.1038/nrm.2017.129 CrossRefPubMedGoogle Scholar
  82. Hernandez-Camacho JD, Bernier M, Lopez-Lluch G, Navas P (2018) Coenzyme Q10 supplementation in aging and disease. Front Physiol 9:44.  https://doi.org/10.3389/fphys.2018.00044 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Holmstrom MH, Iglesias-Gutierrez E, Zierath JR, Garcia-Roves PM (2012) Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes. Am J Physiol Endocrinol Metab 302(6):E731–739.  https://doi.org/10.1152/ajpendo.00159.2011 CrossRefPubMedGoogle Scholar
  84. Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14(10):R115.  https://doi.org/10.1186/gb-2013-14-10-r115 CrossRefPubMedPubMedCentralGoogle Scholar
  85. Huffman DM, Barzilai N (2009) Role of visceral adipose tissue in aging. Biochim Biophys Acta 1790(10):1117–1123.  https://doi.org/10.1016/j.bbagen.2009.01.008 CrossRefPubMedPubMedCentralGoogle Scholar
  86. Imai S, Guarente L (2010) Ten years of NAD-dependent SIR2 family deacetylases: implications for metabolic diseases. Trends Pharmacol Sci 31(5):212–220.  https://doi.org/10.1016/j.tips.2010.02.003 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Inoki K, Zhu T, Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115(5):577–590CrossRefGoogle Scholar
  88. Ishihara M, Urushido M, Hamada K, Matsumoto T, Shimamura Y, Ogata K, Inoue K, Taniguchi Y, Horino T, Fujieda M, Fujimoto S, Terada Y (2013) Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury. Am J Physiol Renal Physiol 305(4):F495–509.  https://doi.org/10.1152/ajprenal.00642.2012 CrossRefPubMedGoogle Scholar
  89. Jager S, Handschin C, St-Pierre J, Spiegelman BM (2007) AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 104(29):12017–12022.  https://doi.org/10.1073/pnas.0705070104 CrossRefPubMedGoogle Scholar
  90. Jagota A, Kalyani D (2010) Effect of melatonin on age induced changes in daily serotonin rhythms in suprachiasmatic nucleus of male Wistar rat. Biogerontology 11(3):299–308.  https://doi.org/10.1007/s10522-009-9248-9 CrossRefPubMedGoogle Scholar
  91. Jheng HF, Tsai PJ, Guo SM, Kuo LH, Chang CS, Su IJ, Chang CR, Tsai YS (2012) Mitochondrial fission contributes to mitochondrial dysfunction and insulin resistance in skeletal muscle. Mol Cell Biol 32(2):309–319.  https://doi.org/10.1128/MCB.05603-11 CrossRefPubMedPubMedCentralGoogle Scholar
  92. Jin SH, Yang JH, Shin BY, Seo K, Shin SM, Cho IJ, Ki SH (2013) Resveratrol inhibits LXRalpha-dependent hepatic lipogenesis through novel antioxidant Sestrin2 gene induction. Toxicol Appl Pharmacol 271(1):95–105.  https://doi.org/10.1016/j.taap.2013.04.023 CrossRefPubMedGoogle Scholar
  93. Joseph SB, Laffitte BA, Patel PH, Watson MA, Matsukuma KE, Walczak R, Collins JL, Osborne TF, Tontonoz P (2002) Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors. J Biol Chem 277(13):11019–11025.  https://doi.org/10.1074/jbc.M111041200 CrossRefPubMedGoogle Scholar
  94. Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106(4):473–481.  https://doi.org/10.1172/JCI10842 CrossRefPubMedPubMedCentralGoogle Scholar
  95. Katic M, Kennedy AR, Leykin I, Norris A, McGettrick A, Gesta S, Russell SJ, Bluher M, Maratos-Flier E, Kahn CR (2007) Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice. Aging Cell 6(6):827–839.  https://doi.org/10.1111/j.1474-9726.2007.00346.x CrossRefPubMedPubMedCentralGoogle Scholar
  96. Kendrick AA, Choudhury M, Rahman SM, McCurdy CE, Friederich M, Van Hove JL, Watson PA, Birdsey N, Bao J, Gius D, Sack MN, Jing E, Kahn CR, Friedman JE, Jonscher KR (2011) Fatty liver is associated with reduced SIRT3 activity and mitochondrial protein hyperacetylation. Biochem J 433(3):505–514.  https://doi.org/10.1042/BJ20100791 CrossRefPubMedPubMedCentralGoogle Scholar
  97. Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE, Rando TA, Richardson A, Schadt EE, Wyss-Coray T, Sierra F (2014) Geroscience: linking aging to chronic disease. Cell 159(4):709–713.  https://doi.org/10.1016/j.cell.2014.10.039 CrossRefPubMedPubMedCentralGoogle Scholar
  98. Khraiwesh H, Lopez-Dominguez JA, Lopez-Lluch G, Navas P, de Cabo R, Ramsey JJ, Villalba JM, Gonzalez-Reyes JA (2013) Alterations of ultrastructural and fission/fusion markers in hepatocyte mitochondria from mice following calorie restriction with different dietary fats. J Gerontol A Biol Sci Med Sci 68(9):1023–1034.  https://doi.org/10.1093/gerona/glt006 CrossRefPubMedPubMedCentralGoogle Scholar
  99. Kim J, Kundu M, Viollet B, Guan KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13(2):132–141.  https://doi.org/10.1038/ncb2152 CrossRefPubMedPubMedCentralGoogle Scholar
  100. Kudo T, Loh DH, Tahara Y, Truong D, Hernandez-Echeagaray E, Colwell CS (2014) Circadian dysfunction in response to in vivo treatment with the mitochondrial toxin 3-nitropropionic acid. ASN Neuro 6(1):e00133.  https://doi.org/10.1042/AN20130042 CrossRefPubMedPubMedCentralGoogle Scholar
  101. Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, Araki S, Sugimoto T, Haneda M, Kashiwagi A, Koya D (2010) Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 120(4):1043–1055.  https://doi.org/10.1172/JCI41376 CrossRefPubMedPubMedCentralGoogle Scholar
  102. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127(6):1109–1122.  https://doi.org/10.1016/j.cell.2006.11.013 CrossRefPubMedGoogle Scholar
  103. Lambert AJ, Brand MD (2009) Reactive oxygen species production by mitochondria. Methods Mol Biol 554:165–181.  https://doi.org/10.1007/978-1-59745-521-3_11 CrossRefPubMedGoogle Scholar
  104. Lane RK, Hilsabeck T, Rea SL (2015) The role of mitochondrial dysfunction in age-related diseases. Biochim Biophys Acta 11:1387–1400.  https://doi.org/10.1016/j.bbabio.2015.05.021 CrossRefGoogle Scholar
  105. Lapinska K, Faria G, McGonagle S, Macumber KM, Heerboth S, Sarkar S (2018) Cancer progenitor cells: the result of an epigenetic event? Anticancer Res 38(1):1–6.  https://doi.org/10.21873/anticanres.12184 CrossRefPubMedGoogle Scholar
  106. Laplante M, Sabatini DM (2009) mTOR signaling at a glance. J Cell Sci 122(Pt 20):3589–3594.  https://doi.org/10.1242/jcs.051011 CrossRefPubMedPubMedCentralGoogle Scholar
  107. Lee S, Jeong SY, Lim WC, Kim S, Park YY, Sun X, Youle RJ, Cho H (2007) Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence. J Biol Chem 282(31):22977–22983.  https://doi.org/10.1074/jbc.M700679200 CrossRefPubMedGoogle Scholar
  108. Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, Ocorr K, Ellisman MH, Bodmer R, Bier E, Karin M (2010) Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327(5970):1223–1228.  https://doi.org/10.1126/science.1182228 CrossRefPubMedPubMedCentralGoogle Scholar
  109. Lee TH, Pastorino L, Lu KP (2011) Peptidyl-prolyl cis-trans isomerase Pin1 in ageing, cancer and Alzheimer disease. Expert Rev Mol Med 13:e21.  https://doi.org/10.1017/S1462399411001906 CrossRefPubMedGoogle Scholar
  110. Lee JH, Budanov AV, Talukdar S, Park EJ, Park HL, Park HW, Bandyopadhyay G, Li N, Aghajan M, Jang I, Wolfe AM, Perkins GA, Ellisman MH, Bier E, Scadeng M, Foretz M, Viollet B, Olefsky J, Karin M (2012) Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab 16(3):311–321.  https://doi.org/10.1016/j.cmet.2012.08.004 CrossRefPubMedPubMedCentralGoogle Scholar
  111. Lee JH, Budanov AV, Karin M (2013) Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab 18(6):792–801.  https://doi.org/10.1016/j.cmet.2013.08.018 CrossRefPubMedGoogle Scholar
  112. Leenen FA, Muller CP, Turner JD (2016) DNA methylation: conducting the orchestra from exposure to phenotype? Clin Epigenetics 8:92.  https://doi.org/10.1186/s13148-016-0256-8 CrossRefPubMedPubMedCentralGoogle Scholar
  113. Lenhare L, Crisol BM, Silva VRR, Katashima CK, Cordeiro AV, Pereira KD, Luchessi AD, da Silva ASR, Cintra DE, Moura LP, Pauli JR, Ropelle ER (2017) Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice. Exp Gerontol 97:17–21.  https://doi.org/10.1016/j.exger.2017.07.009 CrossRefPubMedGoogle Scholar
  114. Liesa M, Borda-d’Agua B, Medina-Gomez G, Lelliott CJ, Paz JC, Rojo M, Palacin M, Vidal-Puig A, Zorzano A (2008) Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta. PLoS ONE 3(10):e3613.  https://doi.org/10.1371/journal.pone.0003613 CrossRefPubMedPubMedCentralGoogle Scholar
  115. Liesa M, Palacin M, Zorzano A (2009) Mitochondrial dynamics in mammalian health and disease. Physiol Rev 89(3):799–845.  https://doi.org/10.1152/physrev.00030.2008 CrossRefPubMedGoogle Scholar
  116. Lin YF, Haynes CM (2016) Metabolism and the UPR(mt). Mol Cell 61(5):677–682.  https://doi.org/10.1016/j.molcel.2016.02.004 CrossRefPubMedPubMedCentralGoogle Scholar
  117. Lopez-Lluch G (2017) Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity. Mech Ageing Dev 162:108–121.  https://doi.org/10.1016/j.mad.2016.12.005 CrossRefPubMedGoogle Scholar
  118. Lopez-Lluch G, Navas P (2016) Calorie restriction as an intervention in ageing. J Physiol 594(8):2043–2060.  https://doi.org/10.1113/JP270543 CrossRefPubMedPubMedCentralGoogle Scholar
  119. Lopez-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, Cascajo MV, Allard J, Ingram DK, Navas P, de Cabo R (2006) Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci USA 103(6):1768–1773.  https://doi.org/10.1073/pnas.0510452103 CrossRefPubMedGoogle Scholar
  120. Lopez-Lluch G, Irusta PM, Navas P, de Cabo R (2008) Mitochondrial biogenesis and healthy aging. Exp Gerontol 43(9):813–819.  https://doi.org/10.1016/j.exger.2008.06.014 CrossRefPubMedPubMedCentralGoogle Scholar
  121. Lopez-Lluch G, Rodriguez-Aguilera JC, Santos-Ocana C, Navas P (2010) Is coenzyme Q a key factor in aging? Mech Ageing Dev 131(4):225–235.  https://doi.org/10.1016/j.mad.2010.02.003 CrossRefPubMedGoogle Scholar
  122. Lopez-Lluch G, Santos-Ocana C, Sanchez-Alcazar JA, Fernandez-Ayala DJ, Asencio-Salcedo C, Rodriguez-Aguilera JC, Navas P (2015) Mitochondrial responsibility in ageing process: innocent, suspect or guilty. Biogerontology 16(5):599–620.  https://doi.org/10.1007/s10522-015-9585-9 CrossRefPubMedGoogle Scholar
  123. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217.  https://doi.org/10.1016/j.cell.2013.05.039 CrossRefPubMedPubMedCentralGoogle Scholar
  124. Lourenco AB, Munoz-Jimenez C, Venegas-Caleron M, Artal-Sanz M (2015) Analysis of the effect of the mitochondrial prohibitin complex, a context-dependent modulator of longevity, on the C. elegans metabolome. Biochim Biophys Acta 11:1457–1468.  https://doi.org/10.1016/j.bbabio.2015.06.003 CrossRefGoogle Scholar
  125. Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307(5708):384–387.  https://doi.org/10.1126/science.1104343 CrossRefPubMedGoogle Scholar
  126. Manikonda PK, Jagota A (2012) Melatonin administration differentially affects age-induced alterations in daily rhythms of lipid peroxidation and antioxidant enzymes in male rat liver. Biogerontology 13(5):511–524.  https://doi.org/10.1007/s10522-012-9396-1 CrossRefPubMedGoogle Scholar
  127. Martin-Montalvo A, de Cabo R (2013) Mitochondrial metabolic reprogramming induced by calorie restriction. Antioxid Redox Signal 19(3):310–320.  https://doi.org/10.1089/ars.2012.4866 CrossRefPubMedPubMedCentralGoogle Scholar
  128. Matsumoto AM (2002) Andropause: clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol A Biol Sci Med Sci 57(2):M76–99CrossRefGoogle Scholar
  129. Mattson MP, Moehl K, Ghena N, Schmaedick M, Cheng A (2018) Intermittent metabolic switching, neuroplasticity and brain health. Nat Rev Neurosci 19(2):63–80.  https://doi.org/10.1038/nrn.2017.156 CrossRefPubMedPubMedCentralGoogle Scholar
  130. McKendry J, Breen L, Shad BJ, Greig CA (2018) Muscle morphology and performance in master athletes: a systematic review and meta-analyses. Ageing Res Rev 45:62–82.  https://doi.org/10.1016/j.arr.2018.04.007 CrossRefPubMedGoogle Scholar
  131. Meister P, Schott S, Bedet C, Xiao Y, Rohner S, Bodennec S, Hudry B, Molin L, Solari F, Gasser SM, Palladino F (2011) Caenorhabditis elegans Heterochromatin protein 1 (HPL-2) links developmental plasticity, longevity and lipid metabolism. Genome Biol 12(12):R123.  https://doi.org/10.1186/gb-2011-12-12-r123 CrossRefPubMedPubMedCentralGoogle Scholar
  132. Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH (2006) Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci 61(6):534–540CrossRefGoogle Scholar
  133. Merry BJ (2002) Molecular mechanisms linking calorie restriction and longevity. Int J Biochem Cell Biol 34(11):1340–1354CrossRefGoogle Scholar
  134. Moehle EA, Shen K, Dillin A (2018) Mitochondrial proteostasis in the context of cellular and organismal health and aging. J Biol Chem.  https://doi.org/10.1074/jbc.TM117.000893 CrossRefPubMedGoogle Scholar
  135. Moreno-Loshuertos R, Enriquez JA (2016) Respiratory supercomplexes and the functional segmentation of the CoQ pool. Free Radic Biol Med.  https://doi.org/10.1016/j.freeradbiomed.2016.04.018 CrossRefPubMedGoogle Scholar
  136. Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, Rinfret S, Schiffrin EL, Eisenberg MJ (2010) The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 56(14):1113–1132.  https://doi.org/10.1016/j.jacc.2010.05.034 CrossRefPubMedGoogle Scholar
  137. Mourier A, Motori E, Brandt T, Lagouge M, Atanassov I, Galinier A, Rappl G, Brodesser S, Hultenby K, Dieterich C, Larsson NG (2015) Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels. J Cell Biol 208(4):429–442.  https://doi.org/10.1083/jcb.201411100 CrossRefPubMedPubMedCentralGoogle Scholar
  138. Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi S, Kurihara H, Uchida T, Asano T (2011) Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with insulin receptor substrate-1 and enhances insulin actions and adipogenesis. J Biol Chem 286(23):20812–20822.  https://doi.org/10.1074/jbc.M110.206904 CrossRefPubMedPubMedCentralGoogle Scholar
  139. Nakatsu Y, Iwashita M, Sakoda H, Ono H, Nagata K, Matsunaga Y, Fukushima T, Fujishiro M, Kushiyama A, Kamata H, Takahashi S, Katagiri H, Honda H, Kiyonari H, Uchida T, Asano T (2015) Prolyl isomerase Pin1 negatively regulates AMP-activated protein kinase (AMPK) by associating with the CBS domain in the gamma subunit. J Biol Chem 290(40):24255–24266.  https://doi.org/10.1074/jbc.M115.658559 CrossRefPubMedPubMedCentralGoogle Scholar
  140. Naon D, Zaninello M, Giacomello M, Varanita T, Grespi F, Lakshminaranayan S, Serafini A, Semenzato M, Herkenne S, Hernandez-Alvarez MI, Zorzano A, De Stefani D, Dorn GW 2nd, Scorrano L (2016) Critical reappraisal confirms that Mitofusin 2 is an endoplasmic reticulum-mitochondria tether. Proc Natl Acad Sci USA 113(40):11249–11254.  https://doi.org/10.1073/pnas.1606786113 CrossRefPubMedGoogle Scholar
  141. Nemoto S, Fergusson MM, Finkel T (2005) SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem 280(16):16456–16460.  https://doi.org/10.1074/jbc.M501485200 CrossRefPubMedGoogle Scholar
  142. Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, Carruba MO (2005) Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310(5746):314–317.  https://doi.org/10.1126/science.1117728 CrossRefPubMedGoogle Scholar
  143. Olichon A, Emorine LJ, Descoins E, Pelloquin L, Brichese L, Gas N, Guillou E, Delettre C, Valette A, Hamel CP, Ducommun B, Lenaers G, Belenguer P (2002) The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett 523(1–3):171–176CrossRefGoogle Scholar
  144. Page MM, Robb EL, Salway KD, Stuart JA (2010) Mitochondrial redox metabolism: aging, longevity and dietary effects. Mech Ageing Dev 131(4):242–252.  https://doi.org/10.1016/j.mad.2010.02.005 CrossRefPubMedGoogle Scholar
  145. Palacios OM, Carmona JJ, Michan S, Chen KY, Manabe Y, Ward JL 3rd, Goodyear LJ, Tong Q (2009) Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY) 1(9):771–783CrossRefGoogle Scholar
  146. Palikaras K, Lionaki E, Tavernarakis N (2015) Coupling mitogenesis and mitophagy for longevity. Autophagy 11(8):1428–1430.  https://doi.org/10.1080/15548627.2015.1061172 CrossRefPubMedPubMedCentralGoogle Scholar
  147. Park YY, Lee S, Karbowski M, Neutzner A, Youle RJ, Cho H (2010) Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1. J Cell Sci 123(Pt 4):619–626.  https://doi.org/10.1242/jcs.061481 CrossRefPubMedPubMedCentralGoogle Scholar
  148. Pastore S, Hood DA (2013) Endurance training ameliorates the metabolic and performance characteristics of circadian Clock mutant mice. J Appl Physiol 114(8):1076–1084.  https://doi.org/10.1152/japplphysiol.01505.2012 CrossRefPubMedGoogle Scholar
  149. Patti ME, Corvera S (2010) The role of mitochondria in the pathogenesis of type 2 diabetes. Endocr Rev 31(3):364–395.  https://doi.org/10.1210/er.2009-0027 CrossRefPubMedPubMedCentralGoogle Scholar
  150. Payne BA, Chinnery PF (2015) Mitochondrial dysfunction in aging: much progress but many unresolved questions. Biochim Biophys Acta 11:1347–1353.  https://doi.org/10.1016/j.bbabio.2015.05.022 CrossRefGoogle Scholar
  151. Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA, Ilkayeva O, Marcheva B, Kobayashi Y, Omura C, Levine DC, Bacsik DJ, Gius D, Newgard CB, Goetzman E, Chandel NS, Denu JM, Mrksich M, Bass J (2013) Circadian clock NAD + cycle drives mitochondrial oxidative metabolism in mice. Science 342(6158):1243417.  https://doi.org/10.1126/science.1243417 CrossRefPubMedPubMedCentralGoogle Scholar
  152. Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, Palacin M, Zorzano A (2005) The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet 14(11):1405–1415.  https://doi.org/10.1093/hmg/ddi149 CrossRefPubMedGoogle Scholar
  153. Qiu X, Brown K, Hirschey MD, Verdin E, Chen D (2010) Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab 12(6):662–667.  https://doi.org/10.1016/j.cmet.2010.11.015 CrossRefPubMedGoogle Scholar
  154. Rai N, Venugopalan G, Pradhan R, Ambastha A, Upadhyay AD, Dwivedi S, Dey AB, Dey S (2018) Exploration of novel anti-oxidant protein sestrin in frailty syndrome in elderly. Aging Dis 9(2):220–227.  https://doi.org/10.14336/AD.2017.0423 CrossRefPubMedPubMedCentralGoogle Scholar
  155. Ramadori G, Coppari R (2010) Pharmacological manipulations of CNS sirtuins: potential effects on metabolic homeostasis. Pharmacol Res 62(1):48–54.  https://doi.org/10.1016/j.phrs.2010.02.002 CrossRefPubMedPubMedCentralGoogle Scholar
  156. Ramadori G, Lee CE, Bookout AL, Lee S, Williams KW, Anderson J, Elmquist JK, Coppari R (2008) Brain SIRT1: anatomical distribution and regulation by energy availability. J Neurosci 28(40):9989–9996.  https://doi.org/10.1523/JNEUROSCI.3257-08.2008 CrossRefPubMedPubMedCentralGoogle Scholar
  157. Rauthan M, Ranji P, Aguilera Pradenas N, Pitot C, Pilon M (2013) The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway. Proc Natl Acad Sci USA 110(15):5981–5986.  https://doi.org/10.1073/pnas.1218778110 CrossRefPubMedGoogle Scholar
  158. Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB, Group CS (2015) A 2-year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity. J Gerontol A Biol Sci Med Sci 70(9):1097–1104.  https://doi.org/10.1093/gerona/glv057 CrossRefPubMedPubMedCentralGoogle Scholar
  159. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ (2000) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors. LXRalpha and LXRbeta. Genes Dev 14(22):2819–2830CrossRefGoogle Scholar
  160. Riera CE, Merkwirth C, De Magalhaes Filho CD, Dillin A (2016) Signaling networks determining life span. Annu Rev Biochem 85:35–64.  https://doi.org/10.1146/annurev-biochem-060815-014451 CrossRefPubMedGoogle Scholar
  161. Roberts MN, Wallace MA, Tomilov AA, Zhou Z, Marcotte GR, Tran D, Perez G, Gutierrez-Casado E, Koike S, Knotts TA, Imai DM, Griffey SM, Kim K, Hagopian K, McMackin MZ, Haj FG, Baar K, Cortopassi GA, Ramsey JJ, Lopez-Dominguez JA (2018) A ketogenic diet extends longevity and healthspan in adult mice. Cell Metab 27(5):1156.  https://doi.org/10.1016/j.cmet.2018.04.005 CrossRefPubMedGoogle Scholar
  162. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434(7029):113–118.  https://doi.org/10.1038/nature03354 CrossRefPubMedGoogle Scholar
  163. Rodriguez-Bies E, Navas P, Lopez-Lluch G (2015) Age-dependent effect of every-other-day feeding and aerobic exercise in ubiquinone levels and related antioxidant activities in mice muscle. J Gerontol A Biol Sci Med Sci 70(1):33–43.  https://doi.org/10.1093/gerona/glu002 CrossRefPubMedGoogle Scholar
  164. Romanello V, Sandri M (2015) Mitochondrial quality control and muscle mass maintenance. Front Physiol 6:422.  https://doi.org/10.3389/fphys.2015.00422 CrossRefPubMedGoogle Scholar
  165. Ruiz R, Perez-Villegas EM, Manuel Carrion A (2016) AMPK function in aging process. Curr Drug Targets 17(8):932–941CrossRefGoogle Scholar
  166. Ryan BJ, Hoek S, Fon EA, Wade-Martins R (2015) Mitochondrial dysfunction and mitophagy in Parkinson’s: from familial to sporadic disease. Trends Biochem Sci 40(4):200–210.  https://doi.org/10.1016/j.tibs.2015.02.003 CrossRefPubMedGoogle Scholar
  167. Samant SA, Zhang HJ, Hong Z, Pillai VB, Sundaresan NR, Wolfgeher D, Archer SL, Chan DC, Gupta MP (2014) SIRT3 deacetylates and activates OPA1 to regulate mitochondrial dynamics during stress. Mol Cell Biol 34(5):807–819.  https://doi.org/10.1128/MCB.01483-13 CrossRefPubMedPubMedCentralGoogle Scholar
  168. Santa-Cruz Calvo S, Navas P, López-Lluch G (2012) Sirtuin-dependent meabolic control and its role in the aging process. In: Clark KB (ed) Bioenergetics. InTech, Rijeka, pp 95–120Google Scholar
  169. Santel A, Frank S (2008) Shaping mitochondria: the complex posttranslational regulation of the mitochondrial fission protein DRP1. IUBMB Life 60(7):448–455.  https://doi.org/10.1002/iub.71 CrossRefPubMedGoogle Scholar
  170. Schottl T, Kappler L, Fromme T, Klingenspor M (2015) Limited OXPHOS capacity in white adipocytes is a hallmark of obesity in laboratory mice irrespective of the glucose tolerance status. Mol Metab 4(9):631–642.  https://doi.org/10.1016/j.molmet.2015.07.001 CrossRefPubMedPubMedCentralGoogle Scholar
  171. Schubeler D (2015) Function and information content of DNA methylation. Nature 517(7534):321–326.  https://doi.org/10.1038/nature14192 CrossRefPubMedGoogle Scholar
  172. Scialo F, Sriram A, Fernandez-Ayala D, Gubina N, Lohmus M, Nelson G, Logan A, Cooper HM, Navas P, Enriquez JA, Murphy MP, Sanz A (2016) Mitochondrial ROS produced via reverse electron transport extend animal lifespan. Cell Metab 23(4):725–734.  https://doi.org/10.1016/j.cmet.2016.03.009 CrossRefPubMedPubMedCentralGoogle Scholar
  173. Scrima R, Cela O, Merla G, Augello B, Rubino R, Quarato G, Fugetto S, Menga M, Fuhr L, Relogio A, Piccoli C, Mazzoccoli G, Capitanio N (2016) Clock-genes and mitochondrial respiratory activity: evidence of a reciprocal interplay. Biochim Biophys Acta 8:1344–1351.  https://doi.org/10.1016/j.bbabio.2016.03.035 CrossRefGoogle Scholar
  174. Sebastian D, Palacin M, Zorzano A (2017) Mitochondrial dynamics: coupling mitochondrial fitness with healthy aging. Trends Mol Med 23(3):201–215.  https://doi.org/10.1016/j.molmed.2017.01.003 CrossRefPubMedGoogle Scholar
  175. Shaw JE, Zimmet PZ, George K, Alberti MM (2005) Metabolic syndrome-do we really need a new definition? Metab Syndr Relat Disord 3(3):191–193.  https://doi.org/10.1089/met.2005.3.191 CrossRefPubMedGoogle Scholar
  176. Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci USA 102(15):5618–5623.  https://doi.org/10.1073/pnas.0501559102 CrossRefPubMedGoogle Scholar
  177. Smirnova E, Griparic L, Shurland DL, van der Bliek AM (2001) Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell 12(8):2245–2256CrossRefGoogle Scholar
  178. Son C, Hosoda K, Ishihara K, Bevilacqua L, Masuzaki H, Fushiki T, Harper ME, Nakao K (2004) Reduction of diet-induced obesity in transgenic mice overexpressing uncoupling protein 3 in skeletal muscle. Diabetologia 47(1):47–54.  https://doi.org/10.1007/s00125-003-1272-8 CrossRefPubMedGoogle Scholar
  179. Soriano FX, Liesa M, Bach D, Chan DC, Palacin M, Zorzano A (2006) Evidence for a mitochondrial regulatory pathway defined by peroxisome proliferator-activated receptor-gamma coactivator-1 alpha, estrogen-related receptor-alpha, and mitofusin 2. Diabetes 55(6):1783–1791.  https://doi.org/10.2337/db05-0509 CrossRefPubMedGoogle Scholar
  180. Sousa JS, D’Imprima E, Vonck J (2018) Mitochondrial respiratory chain complexes. Subcell Biochem 87:167–227.  https://doi.org/10.1007/978-981-10-7757-9_7 CrossRefPubMedGoogle Scholar
  181. Steinberg GR, O’Neill HM, Dzamko NL, Galic S, Naim T, Koopman R, Jorgensen SB, Honeyman J, Hewitt K, Chen ZP, Schertzer JD, Scott JW, Koentgen F, Lynch GS, Watt MJ, van Denderen BJ, Campbell DJ, Kemp BE (2010) Whole body deletion of AMP-activated protein kinase {beta}2 reduces muscle AMPK activity and exercise capacity. J Biol Chem 285(48):37198–37209.  https://doi.org/10.1074/jbc.M110.102434 CrossRefPubMedPubMedCentralGoogle Scholar
  182. Storlien L, Oakes ND, Kelley DE (2004) Metabolic flexibility. Proc Nutr Soc 63(2):363–368.  https://doi.org/10.1079/PNS2004349 CrossRefPubMedGoogle Scholar
  183. Sundstrom J, Riserus U, Byberg L, Zethelius B, Lithell H, Lind L (2006) Clinical value of the metabolic syndrome for long term prediction of total and cardiovascular mortality: prospective, population based cohort study. BMJ 332(7546):878–882.  https://doi.org/10.1136/bmj.38766.624097.1F CrossRefPubMedPubMedCentralGoogle Scholar
  184. Szafranski K, Mekhail K (2014) The fine line between lifespan extension and shortening in response to caloric restriction. Nucleus 5(1):56–65.  https://doi.org/10.4161/nucl.27929 CrossRefPubMedPubMedCentralGoogle Scholar
  185. Tao R, Xiong X, Liangpunsakul S, Dong XC (2015) Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes 64(4):1211–1223.  https://doi.org/10.2337/db14-0539 CrossRefPubMedGoogle Scholar
  186. Tatar M, Sedivy JM (2016) Mitochondria: masters of epigenetics. Cell 165(5):1052–1054.  https://doi.org/10.1016/j.cell.2016.05.021 CrossRefPubMedPubMedCentralGoogle Scholar
  187. Theiss AL, Vijay-Kumar M, Obertone TS, Jones DP, Hansen JM, Gewirtz AT, Merlin D, Sitaraman SV (2009) Prohibitin is a novel regulator of antioxidant response that attenuates colonic inflammation in mice. Gastroenterology 137(1):199–208.  https://doi.org/10.1053/j.gastro.2009.03.033 CrossRefPubMedPubMedCentralGoogle Scholar
  188. Tian Y, Garcia G, Bian Q, Steffen KK, Joe L, Wolff S, Meyer BJ, Dillin A (2016) Mitochondrial stress induces chromatin reorganization to promote longevity and UPR(mt). Cell 165(5):1197–1208.  https://doi.org/10.1016/j.cell.2016.04.011 CrossRefPubMedPubMedCentralGoogle Scholar
  189. Toledo FG, Goodpaster BH (2013) The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging. Mol Cell Endocrinol 379(1–2):30–34.  https://doi.org/10.1016/j.mce.2013.06.018 CrossRefPubMedGoogle Scholar
  190. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, Alroy J, Wu M, Py BF, Yuan J, Deeney JT, Corkey BE, Shirihai OS (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27(2):433–446.  https://doi.org/10.1038/sj.emboj.7601963 CrossRefPubMedPubMedCentralGoogle Scholar
  191. Valli H, Ahmad S, Chadda KR, Al-Hadithi A, Grace AA, Jeevaratnam K, Huang CL (2017) Age-dependent atrial arrhythmic phenotype secondary to mitochondrial dysfunction in Pgc-1beta deficient murine hearts. Mech Ageing Dev 167:30–45.  https://doi.org/10.1016/j.mad.2017.09.002 CrossRefPubMedPubMedCentralGoogle Scholar
  192. Viana-Huete V, Guillen C, Garcia G, Fernandez S, Garcia-Aguilar A, Kahn CR, Benito M (2018) Male brown fat-specific double knockout of IGFIR/IR: atrophy, mitochondrial fission failure, impaired thermogenesis, and obesity. Endocrinology 159(1):323–340.  https://doi.org/10.1210/en.2017-00738 CrossRefPubMedGoogle Scholar
  193. Vina J, Gomez-Cabrera MC, Borras C, Froio T, Sanchis-Gomar F, Martinez-Bello VE, Pallardo FV (2009) Mitochondrial biogenesis in exercise and in ageing. Adv Drug Deliv Rev 61(14):1369–1374.  https://doi.org/10.1016/j.addr.2009.06.006 CrossRefPubMedGoogle Scholar
  194. Wallace DC (2012) Mitochondria and cancer. Nat Rev Cancer 12(10):685–698.  https://doi.org/10.1038/nrc3365 CrossRefPubMedPubMedCentralGoogle Scholar
  195. Wang L, Ishihara T, Ibayashi Y, Tatsushima K, Setoyama D, Hanada Y, Takeichi Y, Sakamoto S, Yokota S, Mihara K, Kang D, Ishihara N, Takayanagi R, Nomura M (2015) Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration. Diabetologia 58(10):2371–2380.  https://doi.org/10.1007/s00125-015-3704-7 CrossRefPubMedGoogle Scholar
  196. Wang M, Xu Y, Liu J, Ye J, Yuan W, Jiang H, Wang Z, Jiang H, Wan J (2017) Recent insights into the biological functions of sestrins in health and disease. Cell Physiol Biochem 43(5):1731–1741.  https://doi.org/10.1159/000484060 CrossRefPubMedGoogle Scholar
  197. Weber TA, Reichert AS (2010) Impaired quality control of mitochondria: aging from a new perspective. Exp Gerontol 45(7–8):503–511.  https://doi.org/10.1016/j.exger.2010.03.018 CrossRefPubMedGoogle Scholar
  198. Weinert D (2010) Circadian temperature variation and ageing. Ageing Res Rev 9(1):51–60.  https://doi.org/10.1016/j.arr.2009.07.003 CrossRefPubMedGoogle Scholar
  199. Willcox BJ, Willcox DC (2014) Caloric restriction, caloric restriction mimetics, and healthy aging in Okinawa: controversies and clinical implications. Curr Opin Clin Nutr Metab Care 17(1):51–58.  https://doi.org/10.1097/MCO.0000000000000019 CrossRefPubMedPubMedCentralGoogle Scholar
  200. Wroblewski AP, Amati F, Smiley MA, Goodpaster B, Wright V (2011) Chronic exercise preserves lean muscle mass in masters athletes. Phys Sportsmed 39(3):172–178.  https://doi.org/10.3810/psm.2011.09.1933 CrossRefPubMedGoogle Scholar
  201. Yang YL, Loh KS, Liou BY, Chu IH, Kuo CJ, Chen HD, Chen CS (2013) SESN-1 is a positive regulator of lifespan in Caenorhabditis elegans. Exp Gerontol 48(3):371–379.  https://doi.org/10.1016/j.exger.2012.12.011 CrossRefPubMedGoogle Scholar
  202. Yoon Y, Krueger EW, Oswald BJ, McNiven MA (2003) The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 23(15):5409–5420CrossRefGoogle Scholar
  203. Yoon YS, Yoon DS, Lim IK, Yoon SH, Chung HY, Rojo M, Malka F, Jou MJ, Martinou JC, Yoon G (2006) Formation of elongated giant mitochondria in DFO-induced cellular senescence: involvement of enhanced fusion process through modulation of Fis1. J Cell Physiol 209(2):468–480.  https://doi.org/10.1002/jcp.20753 CrossRefPubMedGoogle Scholar
  204. Zampieri M, Ciccarone F, Calabrese R, Franceschi C, Burkle A, Caiafa P (2015) Reconfiguration of DNA methylation in aging. Mech Ageing Dev 151:60–70.  https://doi.org/10.1016/j.mad.2015.02.002 CrossRefPubMedGoogle Scholar
  205. Zeng N, D’Souza RF, Mitchell CJ, Cameron-Smith D (2018) Sestrins are differentially expressed with age in the skeletal muscle of men: a cross-sectional analysis. Exp Gerontol.  https://doi.org/10.1016/j.exger.2018.05.006 CrossRefPubMedGoogle Scholar
  206. Ziegler DV, Wiley CD, Velarde MC (2015) Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging. Aging Cell 14(1):1–7.  https://doi.org/10.1111/acel.12287 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Centro Andaluz de Biología del Desarrollo, CABD-CSIC, CIBERER, Instituto de Salud Carlos IIIUniversidad Pablo de OlavideSevilleSpain

Personalised recommendations