Skip to main content
SpringerLink
Log in

Targeting Mitochondria and Redox Dyshomeostasis in Brain Ageing: An Update

  • Chapter
  • First Online:
Redox Signaling and Biomarkers in Ageing

Part of the book series: Healthy Ageing and Longevity ((HAL,volume 15))

Abstract

The increase in life expectancy is one of the highest accomplishments of humankind. Yet, this situation is also one of the most challenging public health issues. Despite the inevitable advancement of biological age, the deterioration of physiological homeostasis is variable and a better knowledge of the molecular mechanisms behind the complexity of the ageing process is a main priority of present societies. As with other organs, ageing induces a significant decrement in the functional capabilities of the brain and the majority of the aged population are confronted with the co-occurrence of diverse brain disorders like neurodegenerative diseases. As substantiated in a vast body of evidence, mitochondria are powerful organelles that not only enable our existence but also the disruption of its function is theorized to have a causative role in physiological and pathological brain ageing. With a focus on mitochondria and associated oxidative stress, we review relevant literature on altered mitochondrial function in physiological and pathological brain ageing, namely in Alzheimer’s and Parkinson’s diseases. The outcomes of mitochondrial medicine targeted to directly manage mitochondrial and oxidative dyshomeostasis will also be discussed. Also, the efficacy of lifestyle modifications and pharmacological strategies will be reviewed as amenable interventions in brain ageing research.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Alexander JF, Seua AV, Arroyo LD, Ray PR, Wangzhou A, Heibeta-Luckemann L, Schedlowski M, Price TJ, Kavelaars A, Heijnen CJ (2021) Nasal administration of mitochondria reverses chemotherapy-induced cognitive deficits. Theranostics 11(7):3109–3130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aluise CD, Robinson RA, Cai J, Pierce WM, Markesbery WR, Butterfield DA (2011) Redox proteomics analysis of brains from subjects with amnestic mild cognitive impairment compared to brains from subjects with preclinical Alzheimer’s disease: insights into memory loss in MCI. J Alzheimers Dis 23(2):257–269

    Article  CAS  PubMed  Google Scholar 

  • Amigo I, Menezes-Filho SL, Luevano-Martinez LA, Chausse B, Kowaltowski AJ (2017) Caloric restriction increases brain mitochondrial calcium retention capacity and protects against excitotoxicity. Aging Cell 16(1):73–81

    Article  CAS  PubMed  Google Scholar 

  • Andrews ZB, Horvath B, Barnstable CJ, Elsworth J, Yang L, Beal MF, Roth RH, Matthews RT, Horvath TL (2005) Uncoupling protein-2 is critical for nigral dopamine cell survival in a mouse model of Parkinson’s disease. J Neurosci 25(1):184–191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andrews ZB, Horvath TL (2009) Uncoupling protein-2 regulates lifespan in mice. Am J Physiol Endocrinol Metab 296(4):E621-627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ansari MA, Scheff SW (2010) Oxidative stress in the progression of Alzheimer disease in the frontal cortex. J Neuropathol Exp Neurol 69(2):155–167

    Article  CAS  PubMed  Google Scholar 

  • Babazadeh A, Mohammadi Vahed F, Jafari SM (2020) Nanocarrier-mediated brain delivery of bioactives for treatment/prevention of neurodegenerative diseases. J Control Release 321:211–221

    Article  CAS  PubMed  Google Scholar 

  • Baloyannis SJ (2006) Mitochondrial alterations in Alzheimer’s disease. J Alzheimers Dis 9(2):119–126

    Article  PubMed  Google Scholar 

  • Barja G (2004) Free radicals and aging. Trends Neurosci 27(10):595–600

    Article  CAS  PubMed  Google Scholar 

  • Barja G, Herrero A (2000) Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals. FASEB J 14(2):312–318

    Article  CAS  PubMed  Google Scholar 

  • Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38(5):515–517

    Article  CAS  PubMed  Google Scholar 

  • Bernardo TC, Marques-Aleixo I, Beleza J, Oliveira PJ, Ascensao A, Magalhaes J (2016) Physical exercise and brain mitochondrial fitness: the possible role against Alzheimer’s disease. Brain Pathol 26(5):648–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bordi M, Berg MJ, Mohan PS, Peterhoff CM, Alldred MJ, Che S, Ginsberg SD, Nixon RA (2016) Autophagy flux in CA1 neurons of Alzheimer hippocampus: increased induction overburdens failing lysosomes to propel neuritic dystrophy. Autophagy 12(12):2467–2483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bose A, Beal MF (2016) Mitochondrial dysfunction in Parkinson’s disease. J Neurochem 139(Suppl 1):216–231

    Article  CAS  PubMed  Google Scholar 

  • Boumezbeur F, Mason GF, de Graaf RA, Behar KL, Cline GW, Shulman GI, Rothman DL, Petersen KF (2010) Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy. J Cereb Blood Flow Metab 30(1):211–221

    Article  CAS  PubMed  Google Scholar 

  • Brand MD (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35(6–7):811–820

    Article  CAS  PubMed  Google Scholar 

  • Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE (2005) Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 57(5):695–703

    Article  CAS  PubMed  Google Scholar 

  • Burte F, Carelli V, Chinnery PF, Yu-Wai-Man P (2015) Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol 11(1):11–24

    Article  CAS  PubMed  Google Scholar 

  • Caccamo A, Majumder S, Richardson A, Strong R, Oddo S (2010) Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem 285(17):13107–13120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai Q, Tammineni P (2016) Alterations in mitochondrial quality control in Alzheimer’s disease. Front Cell Neurosci 10:24

    Article  PubMed  PubMed Central  Google Scholar 

  • Caldeira da Silva CC, Cerqueira FM, Barbosa LF, Medeiros MH, Kowaltowski AJ (2008) Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity. Aging Cell 7(4):552–560

    Article  CAS  PubMed  Google Scholar 

  • Calkins MJ, Manczak M, Mao P, Shirendeb U, Reddy PH (2011) Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer’s disease. Hum Mol Genet 20(23):4515–4529

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calkins MJ, Manczak M, Reddy PH (2012) Mitochondria-targeted antioxidant SS31 prevents amyloid beta-induced mitochondrial abnormalities and synaptic degeneration in Alzheimer’s DISEASE. Pharmaceuticals 5(10):1103–1119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E (2019) From discoveries in ageing research to therapeutics for healthy ageing. Nature 571(7764):183–192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cardoso S, Carvalho C, Correia SC, Seica RM, Moreira PI (2016) Alzheimer’s disease: from mitochondrial perturbations to mitochondrial medicine. Brain Pathol 26(5):632–647

    Article  PubMed  PubMed Central  Google Scholar 

  • Cardoso S, Correia S, Carvalho C, Candeias E, Placido AI, Duarte AI, Seica RM, Moreira PI et al (2015) Perspectives on mitochondrial uncoupling proteins-mediated neuroprotection. J Bioenerg Biomembr 47(1–2):119–131

    Article  CAS  PubMed  Google Scholar 

  • Carroll MA (2018) Cognitive aging and changes in brain morphology. Top Geriatr Rehabil 34(1):1–7. https://doi.org/10.1097/TGR.0000000000000169

  • Carvalho C, Cardoso S, Correia SC, Santos RX, Santos MS, Baldeiras I, Oliveira CR, Moreira PI (2012) Metabolic alterations induced by sucrose intake and Alzheimer’s disease promote similar brain mitochondrial abnormalities. Diabetes 61(5):1234–1242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castellano CA, Hudon C, Croteau E, Fortier M, St-Pierre V, Vandenberghe C, Nugent S, Tremblay S, Paquet N, Lepage M, Fulop T, Turcotte EE, Dionne IJ, Potvin O, Duchesne S, Cunnane SC (2019) Links between metabolic and structural changes in the brain of cognitively normal older adults: a 4-year longitudinal follow-up. Front Aging Neurosci 11:15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang JC, Wu SL, Liu KH, Chen YH, Chuang CS, Cheng FC, Su HL, Wei YH, Kuo SJ, Liu CS (2016) Allogeneic/xenogeneic transplantation of peptide-labeled mitochondria in Parkinson’s disease: restoration of mitochondria functions and attenuation of 6-hydroxydopamine-induced neurotoxicity. Transl Res 170:40–56 e43

    Google Scholar 

  • Chen H, Zhang SM, Schwarzschild MA, Hernan MA, Ascherio A (2005) Physical activity and the risk of Parkinson disease. Neurology 64(4):664–669

    Article  CAS  PubMed  Google Scholar 

  • Cho JY, Um HS, Kang EB, Cho IH, Kim CH, Cho JS, Hwang DY (2010) The combination of exercise training and alpha-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer’s disease in NSE/APPsw-transgenic mice. Int J Mol Med 25(3):337–346

    Article  CAS  PubMed  Google Scholar 

  • Chomyn A, Attardi G (2003) MtDNA mutations in aging and apoptosis. Biochem Biophys Res Commun 304(3):519–529

    Article  CAS  PubMed  Google Scholar 

  • Choubey V, Safiulina D, Vaarmann A, Cagalinec M, Wareski P, Kuum M, Zharkovsky A, Kaasik A (2011) Mutant A53T alpha-synuclein induces neuronal death by increasing mitochondrial autophagy. J Biol Chem 286(12):10814–10824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Correia SC, Resende R, Moreira PI, Pereira CM (2015) Alzheimer’s disease-related misfolded proteins and dysfunctional organelles on autophagy menu. DNA Cell Biol 34(4):261–273

    Article  CAS  PubMed  Google Scholar 

  • Cox LM, Schafer MJ, Sohn J, Vincentini J, Weiner HL, Ginsberg SD, Blaser MJ (2019) Calorie restriction slows age-related microbiota changes in an Alzheimer’s disease model in female mice. Sci Rep 9(1):17904

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Croteau E, Castellano CA, Fortier M, Bocti C, Fulop T, Paquet N, Cunnane SC (2018) A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer’s disease. Exp Geronto l107:18–26

    Google Scholar 

  • Darios F, Corti O, Lucking CB, Hampe C, Muriel MP, Abbas N, Gu WJ, Hirsch EC, Rooney T, Ruberg M, Brice A (2003) Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death. Hum Mol Genet 12(5):517–526

    Article  CAS  PubMed  Google Scholar 

  • De Felice FG, Ferreira ST (2006) Novel neuroprotective, neuritogenic and anti-amyloidogenic properties of 2,4-dinitrophenol: the gentle face of Janus. IUBMB Life 58(4):185–191

    Article  PubMed  CAS  Google Scholar 

  • De Felice FG, Houzel JC, Garcia-Abreu J, Louzada PR Jr, Afonso RC, Meirelles MN, Lent R, Neto VM, Ferreira ST (2001) Inhibition of Alzheimer’s disease beta-amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols: implications for Alzheimer’s therapy. FASEB J 15(7):1297–1299

    Article  PubMed  CAS  Google Scholar 

  • de la Monte SM, Wands JR (2006) Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer’s disease. J Alzheimers Dis 9(2):167–181

    Article  PubMed  Google Scholar 

  • De la Rosa A, Olaso-Gonzalez G, Arc-Chagnaud C, Millan F, Salvador-Pascual A, Garcia-Lucerga C, Blasco-Lafarga C, Garcia-Dominguez E, Carretero A, Correas AG, Vina J, Gomez-Cabrera MC (2020) Physical exercise in the prevention and treatment of Alzheimer’s disease. JSHS 9(5):394–404

    PubMed  PubMed Central  Google Scholar 

  • de Sousa CV, Sales MM, Rosa TS, Lewis JE, de Andrade RV, Simoes HG (2017) The antioxidant effect of exercise: a systematic review and meta-analysis. Sports Med 47(2):277–293

    Article  PubMed  Google Scholar 

  • Deng H, Dodson MW, Huang H, Guo M (2008) The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci USA 105(38):14503–14508

    Google Scholar 

  • Devi L, Raghavendran V, Prabhu BM, Avadhani NG, Anandatheerthavarada HK (2008) Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain. J Biol Chem 283(14):9089–9100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dietrich MO, Andrews ZB, Horvath TL (2008) Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaptation. J Neurosci 28(42):10766–10771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dolle C, Flones I, Nido GS, Miletic H, Osuagwu N, Kristoffersen S, Lilleng PK, Larsen JP, Tysnes OB, Haugarvoll K, Bindoff LA, Tzoulis C (2016) Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nat Commun 7:13548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dragicevic N, Mamcarz M, Zhu Y, Buzzeo R, Tan J, Arendash GW, Bradshaw PC (2010) Mitochondrial amyloid-beta levels are associated with the extent of mitochondrial dysfunction in different brain regions and the degree of cognitive impairment in Alzheimer’s transgenic mice. J Alzheimers Dis 20(Suppl 2):S535-550

    Article  PubMed  CAS  Google Scholar 

  • Ekstrand MI, Terzioglu M, Galter D, Zhu S, Hofstetter C, Lindqvist E, Thams S, Bergstrand A, Hansson FS, Trifunovic A, Hoffer B, Cullheim S, Mohammed AH, Olson L, Larsson NG (2007) Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons. Proc Natl Acad Sci USA 104 (4):1325–1330

    Google Scholar 

  • Emani SM, Piekarski BL, Harrild D, Del Nido PJ, McCully JD (2017) Autologous mitochondrial transplantation for dysfunction after ischemia-reperfusion injury. J Thorac Cardiovasc Surg 154(1):286–289

    Article  PubMed  Google Scholar 

  • Esteves AR, Arduino DM, Swerdlow RH, Oliveira CR, Cardoso SM (2010) Microtubule depolymerization potentiates alpha-synuclein oligomerization. Front Aging Neurosci 1:5.b

    Google Scholar 

  • Esteves AR, Domingues AF, Ferreira IL, Januario C, Swerdlow RH, Oliveira CR, Cardoso SM (2008) Mitochondrial function in Parkinson’s disease cybrids containing an nt2 neuron-like nuclear background. Mitochondrion 8(3):219–228

    Article  CAS  PubMed  Google Scholar 

  • Esteves AR, Gozes I, Cardoso SM (2014) The rescue of microtubule-dependent traffic recovers mitochondrial function in Parkinson’s disease. Biochim Biophys Acta 1:7–21

    Google Scholar 

  • Esteves AR, Lu J, Rodova M, Onyango I, Lezi E, Dubinsky R, Lyons KE, Pahwa R, Burns JM, Cardoso SM, Swerdlow RH (2010) Mitochondrial respiration and respiration-associated proteins in cell lines created through Parkinson’s subject mitochondrial transfer. J Neurochem 113 (3):674–682.a

    Google Scholar 

  • Fang EF, Hou Y, Palikaras K, Adriaanse BA, Kerr JS, Yang B, Lautrup S, Hasan-Olive MM, Caponio D, Dan X, Rocktaschel P, Croteau DL, Akbari M, Greig NH, Fladby T, Nilsen H, Cader MZ, Mattson MP, Tavernarakis N, Bohr VA (2019) Mitophagy inhibits amyloid-beta and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat Neurosci 22(3):401–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng H, Li C, Liu J, Wang L, Ma J, Li G, Gan L, Shang X, Wu Z (2019) Virtual reality rehabilitation versus conventional physical therapy for improving balance and gait in parkinson’s disease patients: a randomized controlled trial. Med Sci Monit 25:4186–4192

    Article  PubMed  PubMed Central  Google Scholar 

  • Fjell AM, Walhovd KB (2010) Structural brain changes in aging: courses, causes and cognitive consequences. Rev Neurosci 21(3):187–221

    Article  PubMed  Google Scholar 

  • Frederick RL, Shaw JM (2007) Moving mitochondria: establishing distribution of an essential organelle. Traffic 8(12):1668–1675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedland RP, Jagust WJ, Huesman RH, Koss E, Knittel B, Mathis CA, Ober BA, Mazoyer BM, Budinger TF (1989) Regional cerebral glucose transport and utilization in Alzheimer’s disease. Neurology 39(11):1427–1434

    Article  CAS  PubMed  Google Scholar 

  • Gan X, Huang S, Wu L, Wang Y, Hu G, Li G, Zhang H, Yu H, Swerdlow RH, Chen JX (1842) Yan SS (2014) Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer’s disease cybrid cell. Biochim Biophys Acta 2:220–231

    Google Scholar 

  • Garcia-Mesa Y, Lopez-Ramos JC, Gimenez-Llort L, Revilla S, Guerra R, Gruart A, Laferla FM, Cristofol R, Delgado-Garcia JM, Sanfeliu C (2011) Physical exercise protects against Alzheimer’s disease in 3xTg-AD mice. J Alzheimers Dis 24(3):421–454

    Article  PubMed  Google Scholar 

  • Geisler JG, Marosi K, Halpern J, Mattson MP (2017) DNP, mitochondrial uncoupling, and neuroprotection: a little dab’ll do ya. Alzheimers Dement 13(5):582–591

    Article  PubMed  Google Scholar 

  • Ghosh A, Langley MR, Harischandra DS, Neal ML, Jin H, Anantharam V, Joseph J, Brenza T, Narasimhan B, Kanthasamy A, Kalyanaraman B, Kanthasamy AG (2016) Mitoapocynin treatment protects against neuroinflammation and dopaminergic neurodegeneration in a preclinical animal model of Parkinson’s disease. J Neuroimmune Pharmacol 11(2):259–278

    Article  PubMed  PubMed Central  Google Scholar 

  • Gibson GE, Shi Q (2010) A mitocentric view of Alzheimer’s disease suggests multi-faceted treatments. J Alzheimers Dis 20(Suppl 2):S591-607

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gonzalez-Freire M, Diaz-Ruiz A, Hauser D, Martinez-Romero J, Ferrucci L, Bernier M, de Cabo R (2020) The road ahead for health and lifespan interventions. Ageing Res Rev 59:101037

    Google Scholar 

  • Grimm A, Eckert A (2017) Brain aging and neurodegeneration: from a mitochondrial point of view. J Neurochem 143(4):418–431

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimm A, Friedland K, Eckert A (2016) Mitochondrial dysfunction: the missing link between aging and sporadic Alzheimer’s disease. Biogerontology 17(2):281–296

    Article  CAS  PubMed  Google Scholar 

  • Grunewald A, Kumar KR, Sue CM (2019) New insights into the complex role of mitochondria in Parkinson’s disease. Prog Neurobiol 177:73–93

    Article  CAS  PubMed  Google Scholar 

  • Grunewald A, Rygiel KA, Hepplewhite PD, Morris CM, Picard M, Turnbull DM (2016) Mitochondrial DNA depletion in respiratory chain-deficient Parkinson disease neurons. Ann Neurol 79(3):366–378

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Guevara R, Gianotti M, Oliver J, Roca P (2011) Age and sex-related changes in rat brain mitochondrial oxidative status. Exp Geronto l46(11):923–928

    Google Scholar 

  • Guevara R, Santandreu FM, Valle A, Gianotti M, Oliver J, Roca P (2009) Sex-dependent differences in aged rat brain mitochondrial function and oxidative stress. Free Radic Biol Med 46(2):169–175

    Article  CAS  PubMed  Google Scholar 

  • Gusdon AM, Callio J, Distefano G, O’Doherty RM, Goodpaster BH, Coen PM, Chu CT (2017) Exercise increases mitochondrial complex I activity and DRP1 expression in the brains of aged mice. Exp Gerontol 90:1–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 26(1):212–220

    Article  CAS  PubMed  Google Scholar 

  • Hampel H, Prvulovic D, Teipel S, Jessen F, Luckhaus C, Frolich L, Riepe MW, Dodel R, Leyhe T, Bertram L, Hoffmann W, Faltraco F, German Task Force on Alzheimer’s D (2011) The future of Alzheimer’s disease: the next 10 years. Prog Neurobiol 95(4):718–728

    Google Scholar 

  • Hansson Petersen CA, Alikhani N, Behbahani H, Wiehager B, Pavlov PF, Alafuzoff I, Leinonen V, Ito A, Winblad B, Glaser E, Ankarcrona M (2008) The amyloid beta-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae. Proc Natl Acad Sci USA 105 (35):13145–13150

    Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300

    Article  CAS  PubMed  Google Scholar 

  • Harman D (1972) The biologic clock: the mitochondria? J Am Geriatr Soc 20(4):145–147

    Article  CAS  PubMed  Google Scholar 

  • Hauptmann S, Scherping I, Drose S, Brandt U, Schulz KL, Jendrach M, Leuner K, Eckert A, Muller WE (2009) Mitochondrial dysfunction: an early event in Alzheimer pathology accumulates with age in AD transgenic mice. Neurobiol Aging 30(10):1574–1586

    Article  CAS  PubMed  Google Scholar 

  • Hayakawa K, Chan SJ, Mandeville ET, Park JH, Bruzzese M, Montaner J, Arai K, Rosell A, Lo EH (2018) Protective effects of endothelial progenitor cell-derived extracellular mitochondria in brain endothelium. Stem Cells 36(9):1404–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, Ji X, Lo EH (2016) Transfer of mitochondria from astrocytes to neurons after stroke. Nature 535(7613):551–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hayashi Y, Yoshida M, Yamato M, Ide T, Wu Z, Ochi-Shindou M, Kanki T, Kang D, Sunagawa K, Tsutsui H, Nakanishi H (2008) Reverse of age-dependent memory impairment and mitochondrial DNA damage in microglia by an overexpression of human mitochondrial transcription factor a in mice. J Neurosci 28(34):8624–8634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hekimi S, Lapointe J, Wen Y (2011) Taking a “good” look at free radicals in the aging process. Trends Cell Biol 21(10):569–576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirai K, Aliev G, Nunomura A, Fujioka H, Russell RL, Atwood CS, Johnson AB, Kress Y, Vinters HV, Tabaton M, Shimohama S, Cash AD, Siedlak SL, Harris PL, Jones PK, Petersen RB, Perry G, Smith MA (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21(9):3017–3023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirose M, Schilf P, Lange F, Mayer J, Reichart G, Maity P, Johren O, Schwaninger M, Scharffetter-Kochanek K, Sina C, Sadik CD, Kohling R, Miroux B, Ibrahim SM (2016) Uncoupling protein 2 protects mice from aging. Mitochondrion 30:42–50

    Article  CAS  PubMed  Google Scholar 

  • Ho PW, Chu AC, Kwok KH, Kung MH, Ramsden DB, Ho SL (2006) Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells: effects on MPP+-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity. J Neurosci Res 84(6):1358–1366

    Article  CAS  PubMed  Google Scholar 

  • Hogan CL, Mata J, Carstensen LL (2013) Exercise holds immediate benefits for affect and cognition in younger and older adults. Psychol Aging 28(2):587–594

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang L, Nakamura Y, Lo EH, Hayakawa K (2019) Astrocyte signaling in the neurovascular unit after central nervous system injury. Int J Mol Sci 20(2)

    Google Scholar 

  • Iijima-Ando K, Hearn SA, Shenton C, Gatt A, Zhao L, Iijima K (2009) Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer’s disease. PloS one 4(12):e8310

    Google Scholar 

  • Jang YC, Hwang DJ, Koo JH, Um HS, Lee NH, Yeom DC, Lee Y, Cho JY (2018) Association of exercise-induced autophagy upregulation and apoptosis suppression with neuroprotection against pharmacologically induced Parkinson’s disease. J Exerc Nutrition Biochem 22(1):1–8

    Article  PubMed  PubMed Central  Google Scholar 

  • Jezek P, Holendova B, Garlid KD, Jaburek M (2018) Mitochondrial uncoupling proteins: subtle regulators of cellular redox signaling. Antioxid Redox Signal 29(7):667–714

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jia YL, Sun SJ, Chen JH, Jia Q, Huo TT, Chu LF, Bai JT, Yu YJ, Yan XX, Wang JH (2016) SS31, a small molecule antioxidant peptide, attenuates beta-amyloid elevation, mitochondrial/synaptic deterioration and cognitive deficit in SAMP8 mice. Curr Alzheimer Res 13(3):297–306

    Article  CAS  PubMed  Google Scholar 

  • Jiang Q, Yin J, Chen J, Ma X, Wu M, Liu G, Yao K, Tan B, Yin Y (2020) Mitochondria-targeted antioxidants: a step towards disease treatment. Oxid Med Cell Longev 2020:8837893

    Article  PubMed  PubMed Central  Google Scholar 

  • Jin Y, McEwen ML, Nottingham SA, Maragos WF, Dragicevic NB, Sullivan PG, Springer JE (2004) The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord. J Neurotrauma 21(10):1396–1404

    Article  PubMed  Google Scholar 

  • Jun Z, Ibrahim MM, Dezheng G, Bo Y, Qiong W, Yuan Z (2015) UCP2 protects against amyloid beta toxicity and oxidative stress in primary neuronal culture. Biomed Pharmacother 74:211–214

    Article  PubMed  CAS  Google Scholar 

  • Kalpouzos G, Chetelat G, Baron JC, Landeau B, Mevel K, Godeau C, Barre L, Constans JM, Viader F, Eustache F, Desgranges B (2009) Voxel-based mapping of brain gray matter volume and glucose metabolism profiles in normal aging. Neurobiol Aging 30(1):112–124

    Article  CAS  PubMed  Google Scholar 

  • Kamat CD, Gadal S, Mhatre M, Williamson KS, Pye QN, Hensley K (2008) Antioxidants in central nervous system diseases: preclinical promise and translational challenges. J Alzheimers Dis 15(3):473–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kamp F, Exner N, Lutz AK, Wender N, Hegermann J, Brunner B, Nuscher B, Bartels T, Giese A, Beyer K, Eimer S, Winklhofer KF, Haass C (2010) Inhibition of mitochondrial fusion by alpha-synuclein is rescued by PINK1, Parkin and DJ-1. EMBO J 29(20):3571–3589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kandimalla R, Manczak M, Fry D, Suneetha Y, Sesaki H, Reddy PH (2016) Reduced dynamin-related protein 1 protects against phosphorylated Tau-induced mitochondrial dysfunction and synaptic damage in Alzheimer’s disease. Hum Mol Genet 25(22):4881–4897

    CAS  PubMed  PubMed Central  Google Scholar 

  • Karlawish J, Jack CR Jr, Rocca WA, Snyder HM, Carrillo MC (2017) Alzheimer’s disease: the next frontier-special report 2017. Alzheimers Dement 13(4):374–380

    Article  PubMed  Google Scholar 

  • Katsouri L, Parr C, Bogdanovic N, Willem M, Sastre M (2011) PPARgamma co-activator-1alpha (PGC-1alpha) reduces amyloid-beta generation through a PPARgamma-dependent mechanism. J Alzheimers Dis 25(1):151–162

    Article  CAS  PubMed  Google Scholar 

  • Keeney PM, Xie J, Capaldi RA, Bennett JP Jr (2006) Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 26(19):5256–5264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan SM, Cassarino DS, Abramova NN, Keeney PM, Borland MK, Trimmer PA, Krebs CT, Bennett JC, Parks JK, Swerdlow RH, Parker WD Jr, Bennett JP Jr (2000) Alzheimer’s disease cybrids replicate beta-amyloid abnormalities through cell death pathways. Ann Neurol 48(2):148–155

    Article  CAS  PubMed  Google Scholar 

  • Khandelwal PJ, Herman AM, Hoe HS, Rebeck GW, Moussa CE (2011) Parkin mediates beclin-dependent autophagic clearance of defective mitochondria and ubiquitinated Abeta in AD models. Hum Mol Genet 20(11):2091–2102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim RH, Smith PD, Aleyasin H, Hayley S, Mount MP, Pownall S, Wakeham A, You-Ten AJ, Kalia SK, Horne P, Westaway D, Lozano AM, Anisman H, Park DS, Mak TW (2005) Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress. Proc Natl Acad Sci U. S. A. 102 (14):5215–5220

    Google Scholar 

  • Kim-Han JS, Dugan LL (2005) Mitochondrial uncoupling proteins in the central nervous system. Antioxid Redox Signal 7(9–10):1173–1181

    Article  CAS  PubMed  Google Scholar 

  • Kishimoto Y, Johnson J, Fang W, Halpern J, Marosi K, Liu D, Geisler JG, Mattson MP (2020) A mitochondrial uncoupler prodrug protects dopaminergic neurons and improves functional outcome in a mouse model of Parkinson’s disease. Neurobiol Aging 85:123–130

    Article  CAS  PubMed  Google Scholar 

  • Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C, Kowall NW, Khrapko K (2006) Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nat Genet 38(5):518–520

    Article  CAS  PubMed  Google Scholar 

  • Krebiehl G, Ruckerbauer S, Burbulla LF, Kieper N, Maurer B, Waak J, Wolburg H, Gizatullina Z, Gellerich FN, Woitalla D, Riess O, Kahle PJ, Proikas-Cezanne T, Kruger R (2010) Reduced basal autophagy and impaired mitochondrial dynamics due to loss of Parkinson’s disease-associated protein DJ-1. PloS one 5(2):e9367

    Google Scholar 

  • Krige D, Carroll MT, Cooper JM, Marsden CD, Schapira AH (1992) Platelet mitochondrial function in Parkinson’s disease. The Royal Kings and Queens Parkinson Disease Research Group. Ann Neurol 32(6):782–788

    Google Scholar 

  • Kuroda Y, Mitsui T, Kunishige M, Shono M, Akaike M, Azuma H, Matsumoto T (2006) Parkin enhances mitochondrial biogenesis in proliferating cells. Human Mol Genet 15(6):883–895. https://doi.org/10.1093/hmg/ddl006

  • Kurokawa T, Asada S, Nishitani S, Hazeki O (2001) Age-related changes in manganese superoxide dismutase activity in the Cereb Cortexof senescence-accelerated prone and resistant mouse. Neurosci Lett 298(2):135–138

    Article  CAS  PubMed  Google Scholar 

  • Kwok JYY, Kwan JCY, Auyeung M, Mok VCT, Lau CKY, Choi KC, Chan HYL (2019) Effects of mindfulness yoga vs stretching and resistance training exercises on anxiety and depression for people with Parkinson disease: a randomized clinical trial. JAMA Neurol 76(7):755–763

    Article  PubMed  PubMed Central  Google Scholar 

  • Kwok KH, Ho PW, Chu AC, Ho JW, Liu HF, Yiu DC, Chan KH, Kung MH, Ramsden DB, Ho SL (2010) Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity. Free Radic Biol Med 49(6):1023–1035

    Article  CAS  PubMed  Google Scholar 

  • Lai JH, Chen KY, Wu JC, Olson L, Brene S, Huang CZ, Chen YH, Kang SJ, Ma KH, Hoffer BJ, Hsieh TH, Chiang YH (2019) Voluntary exercise delays progressive deterioration of markers of metabolism and behavior in a mouse model of Parkinson’s disease. Brain Res 1720:146301

    Google Scholar 

  • Langley M, Ghosh A, Charli A, Sarkar S, Ay M, Luo J, Zielonka J, Brenza T, Bennett B, Jin H, Ghaisas S, Schlichtmann B, Kim D, Anantharam V, Kanthasamy A, Narasimhan B, Kalyanaraman B, Kanthasamy AG (2017) Mito-apocynin prevents mitochondrial dysfunction, microglial activation, oxidative damage, and progressive neurodegeneration in mitopark transgenic mice. Antioxid Redox Signal 27(14):1048–1066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langston JW (1996) The etiology of Parkinson’s disease with emphasis on the MPTP story. Neurology 47(6 Suppl 3):S153-160

    Article  CAS  PubMed  Google Scholar 

  • Lau YS, Patki G, Das-Panja K, Le WD, Ahmad SO (2011) Neuroprotective effects and mechanisms of exercise in a chronic mouse model of Parkinson’s disease with moderate neurodegeneration. Eur J Neurosci 33(7):1264–1274

    Article  PubMed  PubMed Central  Google Scholar 

  • Laurin D, Verreault R, Lindsay J, MacPherson K, Rockwood K (2001) Physical activity and risk of cognitive impairment and dementia in elderly persons. Arch Neurol 58(3):498–504

    Article  CAS  PubMed  Google Scholar 

  • Lee Y, Heo G, Lee KM, Kim AH, Chung KW, Im E, Chung HY, Lee J (2017) Neuroprotective effects of 2,4-dinitrophenol in an acute model of Parkinson’s disease. Brain Res 1663:184–193

    Article  CAS  PubMed  Google Scholar 

  • Leuner K, Schutt T, Kurz C, Eckert SH, Schiller C, Occhipinti A, Mai S, Jendrach M, Eckert GP, Kruse SE, Palmiter RD, Brandt U, Drose S, Wittig I, Willem M, Haass C, Reichert AS, Muller WE (2012) Mitochondrion-derived reactive oxygen species lead to enhanced amyloid beta formation. Antioxid Redox Signal 16(12):1421–1433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li B, Liang F, Ding X, Yan Q, Zhao Y, Zhang X, Bai Y, Huang T, Xu B (2019) Interval and continuous exercise overcome memory deficits related to beta-Amyloid accumulation through modulating mitochondrial dynamics. Behavioural Brain Res 376:112171

    Google Scholar 

  • Li XC, Hu Y, Wang ZH, Luo Y, Zhang Y, Liu XP, Feng Q, Wang Q, Ye K, Liu GP, Wang JZ (2016) Human wild-type full-length tau accumulation disrupts mitochondrial dynamics and the functions via increasing mitofusins. Sci Rep 6:24756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Okamoto K, Hayashi Y, Sheng M (2004) The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell 119(6):873–887

    Article  CAS  PubMed  Google Scholar 

  • Lin AL, Coman D, Jiang L, Rothman DL, Hyder F (2014) Caloric restriction impedes age-related decline of mitochondrial function and neuronal activity. J Cereb Blood Flow Metab 34(9):1440–1443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu D, Zhang Y, Gharavi R, Park HR, Lee J, Siddiqui S, Telljohann R, Nassar MR, Cutler RG, Becker KG, Mattson MP (2015) The mitochondrial uncoupler DNP triggers brain cell mTOR signaling network reprogramming and CREB pathway up-regulation. J Neurochem 134(4):677–692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Google Scholar 

  • Luchsinger JA, Tang MX, Shea S, Mayeux R (2002) Caloric intake and the risk of Alzheimer disease. Arch Neurol 59(8):1258–1263

    Article  PubMed  Google Scholar 

  • Lunenfeld B, Stratton P (2013) The clinical consequences of an ageing world and preventive strategies. Best Pract Res Clin Obstet Gynaecol 27(5):643–659

    Article  PubMed  PubMed Central  Google Scholar 

  • Luoma PT, Eerola J, Ahola S, Hakonen AH, Hellstrom O, Kivisto KT, Tienari PJ, Suomalainen A (2007) Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease. Neurology 69(11):1152–1159

    Article  CAS  PubMed  Google Scholar 

  • Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science 304(5669):448–452

    Article  CAS  PubMed  Google Scholar 

  • Ma H, Jiang T, Tang W, Ma Z, Pu K, Xu F, Chang H, Zhao G, Gao W, Li Y, Wang Q (2020) Transplantation of platelet-derived mitochondria alleviates cognitive impairment and mitochondrial dysfunction in db/db mice. Clin Sci 134(16):2161–2175

    Article  CAS  Google Scholar 

  • MacAskill AF, Kittler JT (2010) Control of mitochondrial transport and localization in neurons. Trends Cell Biol 20(2):102–112

    Article  CAS  PubMed  Google Scholar 

  • Madreiter-Sokolowski CT, Sokolowski AA, Waldeck-Weiermair M, Malli R, Graier WF (2018) Targeting mitochondria to counteract age-related cellular dysfunction. Genes 9(3)

    Google Scholar 

  • Maiti AK, Spoorthi BC, Saha NC, Panigrahi AK (2018) Mitigating peroxynitrite mediated mitochondrial dysfunction in aged rat brain by mitochondria-targeted antioxidant MitoQ. Biogerontology 19(3–4):271–286

    Article  CAS  PubMed  Google Scholar 

  • Majumder S, Richardson A, Strong R, Oddo S (2011) Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. PloS one 6(9):e25416

    Google Scholar 

  • Manczak M, Calkins MJ, Reddy PH (2011) Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer’s disease: implications for neuronal damage. Hum Mol Genet 20(13):2495–2509

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manczak M, Park BS, Jung Y, Reddy PH (2004) Differential expression of oxidative phosphorylation genes in patients with Alzheimer’s disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med 5(2):147–162

    Article  CAS  PubMed  Google Scholar 

  • Manczak M, Reddy PH (2012) Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer’s disease neurons: implications for mitochondrial dysfunction and neuronal damage. Hum Mol Genet 21(11):2538–2547

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mandal PK, Tripathi M, Sugunan S (2012) Brain oxidative stress: detection and mapping of anti-oxidant marker ‘Glutathione’ in different brain regions of healthy male/female, MCI and Alzheimer patients using non-invasive magnetic resonance spectroscopy. Biochem Biophys Res Commun 417(1):43–48

    Article  CAS  PubMed  Google Scholar 

  • Martin KR, Barrett JC (2002) Reactive oxygen species as double-edged swords in cellular processes: low-dose cell signaling versus high-dose toxicity. Hum Exp Toxicol 21(2):71–75

    Article  CAS  PubMed  Google Scholar 

  • Martin-Maestro P, Gargini R, Perry G, Avila J, Garcia-Escudero V (2016) PARK2 enhancement is able to compensate mitophagy alterations found in sporadic Alzheimer’s disease. Hum Mol Genet 25(4):792–806

    Article  CAS  PubMed  Google Scholar 

  • Maswood N, Young J, Tilmont E, Zhang Z, Gash DM, Gerhardt GA, Grondin R, Roth GS, Mattison J, Lane MA, Carson RE, Cohen RM, Mouton PR, Quigley C, Mattson MP, Ingram DK (2004) Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson’s disease. Proc Natl Acad Sci USA 101 (52):18171–18176

    Google Scholar 

  • Mathew A, Fukuda T, Nagaoka Y, Hasumura T, Morimoto H, Yoshida Y, Maekawa T, Venugopal K, Kumar DS (2012) Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer’s disease. PloS one 7(3):e32616

    Google Scholar 

  • Mattson MP, Arumugam TV (2018) Hallmarks of brain aging: adaptive and pathological modification by metabolic states. Cell Metab 27(6):1176–1199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):15703–15715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mecocci P, Boccardi V, Cecchetti R, Bastiani P, Scamosci M, Ruggiero C, Baroni M (2018) A long journey into aging, brain aging, and Alzheimer’s disease following the oxidative stress tracks. J Alzheimers Dis 62(3):1319–1335

    Article  PubMed  PubMed Central  Google Scholar 

  • Mecocci P, MacGarvey U, Kaufman AE, Koontz D, Shoffner JM, Wallace DC, Beal MF (1993) Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 34(4):609–616

    Article  CAS  PubMed  Google Scholar 

  • Mehta SL, Li PA (2009) Neuroprotective role of mitochondrial uncoupling protein 2 in cerebral stroke. J Cereb Blood Flow Metab 29(6):1069–1078

    Article  CAS  PubMed  Google Scholar 

  • Meulener M, Whitworth AJ, Armstrong-Gold CE, Rizzu P, Heutink P, Wes PD, Pallanck LJ, Bonini NM (2005) Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson’s disease. Curr Bio l15(17):1572–1577

    Google Scholar 

  • Miccheli A, Puccetti C, Capuani G, Di Cocco ME, Giardino L, Calza L, Battaglia A, Battistin L, Conti F (2003) [1-13C]Glucose entry in neuronal and astrocytic intermediary metabolism of aged rats. A study of the effects of nicergoline treatment by 13C NMR spectroscopy. Brain Res 966(1):116–125

    Google Scholar 

  • Michel JP, Sadana R (2017) “Healthy Aging” concepts and measures. J Am Med Dir Assoc 18(6):460–464

    Article  PubMed  Google Scholar 

  • Misko A, Jiang S, Wegorzewska I, Milbrandt J, Baloh RH (2010) Mitofusin 2 is necessary for transport of axonal mitochondria and interacts with the Miro/Milton complex. J Neurosci 30(12):4232–4240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montesanto A, Crocco P, Anfossi M, Smirne N, Puccio G, Colao R, Maletta R, Passarino G, Bruni AC, Rose G (2016) The genetic variability of UCP4 affects the individual susceptibility to late-onset Alzheimer’s disease and modifies the disease’s risk in APOE-varepsilon4 carriers. J Alzheimers Dis 51(4):1265–1274

    Article  CAS  PubMed  Google Scholar 

  • Moreira PI, Duarte AI, Santos MS, Rego AC, Oliveira CR (2009) An integrative view of the role of oxidative stress, mitochondria and insulin in Alzheimer’s disease. J Alzheimers Dis 16(4):741–761

    Article  PubMed  CAS  Google Scholar 

  • Morsci NS, Hall DH, Driscoll M, Sheng ZH (2016) Age-related phasic patterns of mitochondrial maintenance in adult Caenorhabditis elegans neurons. J Neurosci 36(4):1373–1385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mosconi L, Brys M, Glodzik-Sobanska L, De Santi S, Rusinek H, de Leon MJ (2007) Early detection of Alzheimer’s disease using neuroimaging. Exp Gerontol 42(1–2):129–138

    Google Scholar 

  • Mouton PR, Chachich ME, Quigley C, Spangler E, Ingram DK (2009) Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice. Neurosci Lett 46(3):184–187

    Article  CAS  Google Scholar 

  • Mursaleen L, Noble B, Chan SHY, Somavarapu S, Zariwala MG (2020) N-acetylcysteine nanocarriers protect against oxidative stress in a cellular model of Parkinson’s disease. Antioxidants 9(7)

    Google Scholar 

  • Navarro A, Boveris A (2004) Rat brain and liver mitochondria develop oxidative stress and lose enzymatic activities on aging. Am J Physiol Regul Integr Comp 287(5):R1244-1249

    Article  CAS  Google Scholar 

  • Navarro A, Gomez C, Lopez-Cepero JM, Boveris A (2004) Beneficial effects of moderate exercise on mice aging: survival, behavior, oxidative stress, and mitochondrial electron transfer. Am J Physiol Regul Integr Comp 286(3):R505-511

    Article  CAS  Google Scholar 

  • Neves AR, Queiroz JF, Reis S (2016) Brain-targeted delivery of resveratrol using solid lipid nanoparticles functionalized with apolipoprotein E. J Nanobiotechnol 14:27

    Article  CAS  Google Scholar 

  • Ng LF, Gruber J, Cheah IK, Goo CK, Cheong WF, Shui G, Sit KP, Wenk MR, Halliwell B (2014) The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease. Free Radic Biol Med 71:390–401

    Article  CAS  PubMed  Google Scholar 

  • Nitzan K, Benhamron S, Valitsky M, Kesner EE, Lichtenstein M, Ben-Zvi A, Ella E, Segalstein Y, Saada A, Lorberboum-Galski H, Rosenmann H (2019) Mitochondrial transfer ameliorates cognitive deficits, neuronal loss, and gliosis in Alzheimer’s disease Mice. J Alzheimers Dis 72(2):587–604

    Article  CAS  PubMed  Google Scholar 

  • Nunomura A, Tamaoki T, Motohashi N, Nakamura M, McKeel DW Jr, Tabaton M, Lee HG, Smith MA, Perry G, Zhu X (2012) The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. J Neuropathol Exp Neurol 71(3):233–241

    Article  CAS  PubMed  Google Scholar 

  • Oettinghaus B, Schulz JM, Restelli LM, Licci M, Savoia C, Schmidt A, Schmitt K, Grimm A, More L, Hench J, Tolnay M, Eckert A, D’Adamo P, Franken P, Ishihara N, Mihara K, Bischofberger J, Scorrano L, Frank S (2016) Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. Cell Death Differ 23(1):18–28

    Article  CAS  PubMed  Google Scholar 

  • Ozcelik S, Fraser G, Castets P, Schaeffer V, Skachokova Z, Breu K, Clavaguera F, Sinnreich M, Kappos L, Goedert M, Tolnay M, Winkler DT (2013) Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice. PloS one 8(5):e62459

    Google Scholar 

  • Pandya JD, Grondin R, Yonutas HM, Haghnazar H, Gash DM, Zhang Z, Sullivan PG (2015) Decreased mitochondrial bioenergetics and calcium buffering capacity in the basal ganglia correlates with motor deficits in a nonhuman primate model of aging. Neurobiol Aging 36(5):1903–1913

    Article  CAS  PubMed  Google Scholar 

  • Pandya JD, Royland JE, MacPhail RC, Sullivan PG, Kodavanti PR (2016) Age- and brain region-specific differences in mitochondrial bioenergetics in Brown Norway rats. Neurobiol Aging 42:25–34

    Article  CAS  PubMed  Google Scholar 

  • Pardo JV, Lee JT, Sheikh SA, Surerus-Johnson C, Shah H, Munch KR, Carlis JV, Lewis SM, Kuskowski MA, Dysken MW (2007) Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging. Neuroimage 35(3):1231–1237

    Article  PubMed  Google Scholar 

  • Park J, Kim Y, Chung J (2009a) Mitochondrial dysfunction and Parkinson’s disease genes: insights from Drosophila. Dis Model Mech 2(7–8):336–340

    Article  CAS  PubMed  Google Scholar 

  • Park J, Lee G, Chung J (2009b) The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process. Biochem Biophys Res Commun 378(3):518–523

    Article  CAS  PubMed  Google Scholar 

  • Park JH, Hayakawa K (2021) Extracellular mitochondria signals in CNS disorders. Front Cell Dev Biol 9:642853

    Google Scholar 

  • Parker WD Jr, Parks JK, Swerdlow RH (2008) Complex I deficiency in Parkinson’s disease frontal cortex. Brain Res 1189:215–218

    Article  CAS  PubMed  Google Scholar 

  • Patel NV, Gordon MN, Connor KE, Good RA, Engelman RW, Mason J, Morgan DG, Morgan TE, Finch CE (2005) Caloric restriction attenuates Abeta-deposition in Alzheimer transgenic models. Neurobiol Aging 26(7):995–1000

    Article  CAS  PubMed  Google Scholar 

  • Perry RJ, Kim T, Zhang XM, Lee HY, Pesta D, Popov VB, Zhang D, Rahimi Y, Jurczak MJ, Cline GW, Spiegel DA, Shulman GI (2013) Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler. Cell Metab 18(5):740–748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Persson T, Popescu BO, Cedazo-Minguez A (2014) Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxid Med Cell Longev 2014:427318

    Google Scholar 

  • Peskind ER, Li G, Shofer JB, Millard SP, Leverenz JB, Yu CE, Raskind MA, Quinn JF, Galasko DR, Montine TJ (2014) Influence of lifestyle modifications on age-related free radical injury to brain. JAMA Neurol 71(9):1150–1154

    Article  PubMed  PubMed Central  Google Scholar 

  • Picard M, Wallace DC, Burelle Y (2016) The rise of mitochondria in medicine. Mitochondrion 30:105–116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Picca A, Pesce V, Fracasso F, Joseph AM, Leeuwenburgh C, Lezza AM (2013) Aging and calorie restriction oppositely affect mitochondrial biogenesis through TFAM binding at both origins of mitochondrial DNA replication in rat liver. PloS one 8(9):e74644

    Google Scholar 

  • Pope SK, Shue VM, Beck C (2003) Will a healthy lifestyle help prevent Alzheimer’s disease? Annu Rev 24:111–132

    Google Scholar 

  • Pozo Devoto VM, Dimopoulos N, Alloatti M, Pardi MB, Saez TM, Otero MG, Cromberg LE, Marin-Burgin A, Scassa ME, Stokin GB, Schinder AF, Sevlever G, Falzone TL (2017) alphaSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease. Sci Rep 7(1):5042

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Pratico D, Uryu K, Leight S, Trojanoswki JQ, Lee VM (2001) Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 21(12):4183–4187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin W, Haroutunian V, Katsel P, Cardozo CP, Ho L, Buxbaum JD, Pasinetti GM (2009) PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia. Arch Neuro l66(3):352–361

    Google Scholar 

  • Radak Z, Hart N, Sarga L, Koltai E, Atalay M, Ohno H, Boldogh I (2010) Exercise plays a preventive role against Alzheimer’s disease. J Alzheimers Dis 20(3):777–783

    Article  PubMed  Google Scholar 

  • Ramsden DB, Ho PW, Ho JW, Liu HF, So DH, Tse HM, Chan KH, Ho SL (2012) Human neuronal uncoupling proteins 4 and 5 (UCP4 and UCP5): structural properties, regulation, and physiological role in protection against oxidative stress and mitochondrial dysfunction. Brain Behav 2(4):468–478

    Article  PubMed  PubMed Central  Google Scholar 

  • Raza C, Anjum R, Shakeel NUA (2019) Parkinson’s disease: mechanisms, translational models and management strategies. Life Sci 226:77–90

    Article  CAS  PubMed  Google Scholar 

  • Rebrin I, Forster MJ, Sohal RS (2007) Effects of age and caloric intake on glutathione redox state in different brain regions of C57BL/6 and DBA/2 mice. Brain Res 1127(1):10–18

    Article  CAS  PubMed  Google Scholar 

  • Reddy PH, Manczak M, Yin X, Reddy AP (2018) Synergistic protective effects of mitochondrial division inhibitor 1 and mitochondria-targeted small peptide SS31 in Alzheimer’s disease. J Alzheimers Dis 62(4):1549–1565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 e804

    Google Scholar 

  • Resende R, Moreira PI, Proenca T, Deshpande A, Busciglio J, Pereira C, Oliveira CR (2008) Brain oxidative stress in a triple-transgenic mouse model of Alzheimer disease. Free Radic Biol Med 44(12):2051–2057

    Article  CAS  PubMed  Google Scholar 

  • Reutzel M, Grewal R, Dilberger B, Silaidos C, Joppe A, Eckert GP (2020) Cerebral mitochondrial function and cognitive performance during aging: a longitudinal study in NMRI mice. Oxid Med Cell Longev 2020:4060769

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Reynolds GO, Otto MW, Ellis TD, Cronin-Golomb A (2016) The therapeutic potential of exercise to improve mood, cognition, and sleep in Parkinson’s disease. Mov Disord 31(1):23–38

    Article  PubMed  Google Scholar 

  • Rocha EM, De Miranda B, Sanders LH (2018) Alpha-synuclein: pathology, mitochondrial dysfunction and neuroinflammation in Parkinson’s disease. Neurobiol Dis 109(Pt B):249–257

    Article  CAS  PubMed  Google Scholar 

  • Rodolfo C, Campello S, Cecconi F (2018) Mitophagy in neurodegenerative diseases. Neurochem Int 117:156–166

    Article  CAS  PubMed  Google Scholar 

  • Rose G, Crocco P, De Rango F, Montesanto A, Passarino G (2011) Further support to the uncoupling-to-survive theory: the genetic variation of human UCP genes is associated with longevity. PloS one 6(12):e29650

    Google Scholar 

  • Rothfuss O, Fischer H, Hasegawa T, Maisel M, Leitner P, Miesel F, Sharma M, Bornemann A, Berg D, Gasser T, Patenge N (2009) Parkin protects mitochondrial genome integrity and supports mitochondrial DNA repair. Hum Mol Genet 18(20):3832–3850

    Article  CAS  PubMed  Google Scholar 

  • Ryan SM, Kelly AM (2016) Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease. Ageing Res Rev 27:77–92

    Article  CAS  PubMed  Google Scholar 

  • Sadowska-Bartosz I, Bartosz G (2014) Effect of antioxidants supplementation on aging and longevity. BioMed Res Int 2014:404680

    Google Scholar 

  • Salat DH, Buckner RL, Snyder AZ, Greve DN, Desikan RS, Busa E, Morris JC, Dale AM, Fischl B (2004) Thinning of the cereb cortexin aging. Cereb Cortex 14(7):721–730

    Google Scholar 

  • Sampaio-Marques B, Pereira H, Santos AR, Teixeira A, Ludovico P (2018) Caloric restriction rescues yeast cells from alpha-synuclein toxicity through autophagic control of proteostasis. Aging 10(12):3821–3833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santos RX, Correia SC, Zhu X, Smith MA, Moreira PI, Castellani RJ, Nunomura A, Perry G (2013) Mitochondrial DNA oxidative damage and repair in aging and Alzheimer’s disease. Antioxid Redox Signal 18(18):2444–2457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarkar S, Raymick J, Imam S (2016) Neuroprotective and therapeutic strategies against Parkinson’s disease: recent perspectives. Int J Mol Sci 17(6):904

    Article  PubMed Central  CAS  Google Scholar 

  • Schafer MJ, Dolgalev I, Alldred MJ, Heguy A, Ginsberg SD (2015) Calorie restriction suppresses age-dependent hippocampal transcriptional signatures. PloS one 10(7):e0133923

    Google Scholar 

  • Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54(3):823–827

    Article  CAS  PubMed  Google Scholar 

  • Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C (2010) New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 123(Pt 15):2533–2542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shadel GS, Horvath TL (2015) Mitochondrial ROS signaling in organismal homeostasis. Cell 163(3):560–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shanmughapriya S, Langford D, Natarajaseenivasan K (2020) Inter and Intracellular mitochondrial trafficking in health and disease. Ageing Res Rev 62:101128

    Google Scholar 

  • Sheng B, Wang X, Su B, Lee HG, Casadesus G, Perry G, Zhu X (2012) Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease. J Neurochem 120(3):419–429

    Article  CAS  PubMed  Google Scholar 

  • Shi X, Zhao M, Fu C, Fu A (2017) Intravenous administration of mitochondria for treating experimental Parkinson’s disease. Mitochondrion 34:91–100

    Article  CAS  PubMed  Google Scholar 

  • Silva DF, Santana I, Esteves AR, Baldeiras I, Arduino DM, Oliveira CR, Cardoso SM (2013) Prodromal metabolic phenotype in MCI cybrids: implications for Alzheimer’s disease. Curr Alzheimer Res 10(2):180–190

    Article  CAS  PubMed  Google Scholar 

  • Singh-Manoux A, Kivimaki M, Glymour MM, Elbaz A, Berr C, Ebmeier KP, Ferrie JE, Dugravot A (2012) Timing of onset of cognitive decline: results from Whitehall II prospective cohort study. BMJ 344:d7622

    Google Scholar 

  • Snow BJ, Rolfe FL, Lockhart MM, Frampton CM, O'Sullivan JD, Fung V, Smith RA, Murphy MP, Taylor KM, Protect Study G (2010) A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson’s disease. Mov Disord 25(11):1670–1674

    Google Scholar 

  • Solesio ME, Prime TA, Logan A, Murphy MP, Del Mar A-J, Jordan J (1832) Galindo MF (2013) The mitochondria-targeted anti-oxidant MitoQ reduces aspects of mitochondrial fission in the 6-OHDA cell model of Parkinson’s disease. Biochim Biophys Acta 1:174–182

    Google Scholar 

  • Stauch KL, Purnell PR, Fox HS (2014) Aging synaptic mitochondria exhibit dynamic proteomic changes while maintaining bioenergetic function. Aging (albany NY) 6(4):320–334

    Article  CAS  Google Scholar 

  • Sultana R, Perluigi M, Butterfield DA (2013) Lipid peroxidation triggers neurodegeneration: a redox proteomics view into the Alzheimer disease brain. Free Radic Biol Med 62:157–169

    Article  CAS  PubMed  Google Scholar 

  • Sun N, Youle RJ, Finkel T (2016) The mitochondrial basis of aging. Mol Cell 61(5):654–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swerdlow RH (2009) Mitochondrial medicine and the neurodegenerative mitochondriopathies. Pharmaceuticals 2(3):150–167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swerdlow RH, Burns JM, Khan SM (2010) The Alzheimer’s disease mitochondrial cascade hypothesis. J Alzheimers Dis 20(Suppl 2):S265-279

    Article  PubMed  CAS  Google Scholar 

  • Swerdlow RH, Khan SM (2004) A “mitochondrial cascade hypothesis” for sporadic Alzheimer’s disease. Med Hypotheses 63(1):8–20

    Article  CAS  PubMed  Google Scholar 

  • Swomley AM, Butterfield DA (2015) Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics. Arch Toxicol 89(10):1669–1680

    Article  CAS  PubMed  Google Scholar 

  • Tanaka A (2010) Parkin-mediated selective mitochondrial autophagy, mitophagy: Parkin purges damaged organelles from the vital mitochondrial network. FEBS Lett 584(7):1386–1392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tobore TO (2019) On the central role of mitochondria dysfunction and oxidative stress in Alzheimer’s disease. Neurol Sci 40(8):1527–1540

    Article  PubMed  Google Scholar 

  • Tonnies E, Trushina E (2017) Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 57(4):1105–1121

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Venkateshappa C, Harish G, Mahadevan A, Srinivas Bharath MM, Shankar SK (2012) Elevated oxidative stress and decreased antioxidant function in the human hippocampus and frontal cortex with increasing age: implications for neurodegeneration in Alzheimer’s disease. Neurochem Res 37(8):1601–1614

    Article  CAS  PubMed  Google Scholar 

  • Vina J, Borras C, Abdelaziz KM, Garcia-Valles R, Gomez-Cabrera MC (2013) The free radical theory of aging revisited: the cell signaling disruption theory of aging. Antioxid Redox Signal 19(8):779–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vinke EJ, Ikram MA, Vernooij MW (2019) Brain aging: more of the same!? Aging 11(3):849–850

    Article  PubMed  PubMed Central  Google Scholar 

  • Visser PJ, Verhey FR, Hofman PA, Scheltens P, Jolles J (2002) Medial temporal lobe atrophy predicts Alzheimer’s disease in patients with minor cognitive impairment. J Neurol Neurosurg Psychiatry 72(4):491–497

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Perry G, Smith MA, Zhu X (2010) Amyloid-beta-derived diffusible ligands cause impaired axonal transport of mitochondria in neurons. Neurodegener Dis 7(1–3):56–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Su B, Lee HG, Li X, Perry G, Smith MA, Zhu X (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci 29(28):9090–9103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X (2008) Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proc Natl Acad Sci USA 105 (49):19318–19323

    Google Scholar 

  • Wang J, Lei H, Hou J, Liu J (2015) Involvement of oxidative stress in SAMP10 mice with age-related neurodegeneration. Neurol Sci 36(5):743–750

    Article  PubMed  Google Scholar 

  • Wasilewska-Sampaio AP, Silveira MS, Holub O, Goecking R, Gomes FC, Neto VM, Linden R, Ferreira ST, De Felice FG (2005) Neuritogenesis and neuronal differentiation promoted by 2,4-dinitrophenol, a novel anti-amyloidogenic compound. FASEB J 19(12):1627–1636

    Article  CAS  PubMed  Google Scholar 

  • Weidinger A, Kozlov AV (2015) Biological activities of reactive oxygen and nitrogen species: oxidative stress versus signal transduction. Biomolecules 5(2):472–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu B, Jiang M, Peng Q, Li G, Hou Z, Milne GL, Mori S, Alonso R, Geisler JG, Duan W (2017) 2,4 DNP improves motor function, preserves medium spiny neuronal identity, and reduces oxidative stress in a mouse model of Huntington’s disease. Exp Neurol 293:83–90

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Dou Y, Ladiges WC (2020) Adverse neurological effects of short-term sleep deprivation in aging mice are prevented by SS31 peptide. Clocks Sleep 2(3):325–333

    Article  PubMed  PubMed Central  Google Scholar 

  • Wyss-Coray T (2016) Ageing, neurodegeneration and brain rejuvenation. Nature 539(7628):180–186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xi Y, Feng D, Tao K, Wang R, Shi Y, Qin H, Murphy MP, Yang Q, Zhao G (2018) MitoQ protects dopaminergic neurons in a 6-OHDA induced PD model by enhancing Mfn2-dependent mitochondrial fusion via activation of PGC-1alpha. Biochim Biophys Acta Mol Basis Dis 1864(9 Pt B):2859–2870

    Google Scholar 

  • Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Chen H (2010) Physical activities and future risk of Parkinson disease. Neurology 75(4):341–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu S, Zhong M, Zhang L, Wang Y, Zhou Z, Hao Y, Zhang W, Yang X, Wei A, Pei L, Yu Z (2009) Overexpression of Tfam protects mitochondria against beta-amyloid-induced oxidative damage in SH-SY5Y cells. FEBS J 276(14):3800–3809

    Article  CAS  PubMed  Google Scholar 

  • Yang L, Zhao K, Calingasan NY, Luo G, Szeto HH, Beal MF (2009) Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. Antioxid Redox Signal 11(9):2095–2104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yao J, Chen S, Mao Z, Cadenas E, Brinton RD (2011) 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer’s disease. PloS one 6(7):e21788

    Google Scholar 

  • Yao J, Irwin RW, Zhao L, Nilsen J, Hamilton RT, Brinton RD (2009) Mitochondrial bioenergetic deficit precedes Alzheimer’s pathology in female mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 106(34):14670–14675

    Google Scholar 

  • Ye X, Sun X, Starovoytov V, Cai Q (2015) Parkin-mediated mitophagy in mutant hAPP neurons and Alzheimer’s disease patient brains. Hum Mol Genet 24(10):2938–2951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young ML, Franklin JL (2019) The mitochondria-targeted antioxidant MitoQ inhibits memory loss, neuropathology, and extends lifespan in aged 3xTg-AD mice. Mol Cell Neurosci 101:103409

    Google Scholar 

  • Zhao XL, Wang WA, Tan JX, Huang JK, Zhang X, Zhang BZ, Wang YH, YangCheng HY, Zhu HL, Sun XJ, Huang FD (2010) Expression of beta-amyloid induced age-dependent presynaptic and axonal changes in Drosophila. J Neurosci 30(4):1512–1522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Z, Yu Z, Hou Y, Zhang L, Fu A (2020) Improvement of cognitive and motor performance with mitotherapy in aged mice. Int J Biol Sci 16(5):849–858

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zweig JA, Caruso M, Brandes MS, Gray NE (2020) Loss of NRF2 leads to impaired mitochondrial function, decreased synaptic density and exacerbated age-related cognitive deficits. Exp Gerontol 131:110767

    Google Scholar 

Download references

Acknowledgements

Susana Cardoso has a Post-Doctoral Researcher Contract (DL57/2016 #SFRH/BPD/95770/2013) from FCT—Foundation for Science and Technology.

Funding

Funding

The authors’ work is supported by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme, the COMPETE 2020—Operational Programme for Competitiveness and Healthy Aging 2020 (CENTRO-01–0145-FEDER-000012) and by national funds by FCT—Foundation for Science and Technology under the strategic projects UIDB/04539/2020 and UIDP/04539/2020.

Conflict of Interest

All authors declare they have no conflict of interest.

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Author information

Authors and Affiliations

  1. CNC – Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal

    Susana Cardoso & Paula I. Moreira

  2. IIIUC – Institute for Interdisciplinary Research, University of Coimbra, 3004-504, Coimbra, Portugal

    Susana Cardoso

  3. CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504, Coimbra, Portugal

    Susana Cardoso & Paula I. Moreira

  4. Faculty of Medicine, Institute of Physiology, University of Coimbra, 3004-504, Coimbra, Portugal

    Paula I. Moreira

Authors
  1. Susana Cardoso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paula I. Moreira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paula I. Moreira .

Editor information

Editors and Affiliations

  1. Department of Medical Biochemistry Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Ufuk Çakatay

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Cardoso, S., Moreira, P.I. (2022). Targeting Mitochondria and Redox Dyshomeostasis in Brain Ageing: An Update. In: Çakatay, U. (eds) Redox Signaling and Biomarkers in Ageing. Healthy Ageing and Longevity, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-030-84965-8_8

Download citation

Publish with us

Policies and ethics

Search

Navigation