Skip to main content

Advertisement

SpringerLink
Log in

Mitochondrial function, mitochondrial DNA and ageing: a reappraisal

  • SI: Frailty, Ageing and Inflammation
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

The impressive performance of the research in biology of mitochondrion has greatly improved our knowledge on the functions of this organelle and highlighted the influence its functioning has on numerous human phenotypes. In particular, many studies have focused on the involvement of mitochondrion function (and dysfunction) in human ageing. To date, the literature in this specific field of mitochondrial biology is so vast that it is often difficult to properly put new data and new findings in the right context. The present paper aims to review the findings of the last few years in order to outline a general framework to understand how mitochondria can affect ageing and how ageing affects mitochondria.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465

    Article  CAS  PubMed  Google Scholar 

  • Armstrong JS (2006) Mitochondria: a target for cancer therapy. Br J Pharmacol 147:239–248

    Article  CAS  PubMed  Google Scholar 

  • Bandinelli S, Corsi AM, Milaneschi Y, Vazzana R (2010) Frailty and the homeostatic network. Acta Biomed 811(Suppl):15–18

    Google Scholar 

  • Barazzoni R, Short KR, Nair KS (2000) Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart. J Biol Chem 275:3343–3347

    Article  CAS  PubMed  Google Scholar 

  • Barrett TG, Scott-Brown M, Seller A, Bednarz A, Poulton K, Poulton J (2000) The mitochondrial genome in Wolfram syndrome. J Med Genet 37:463–466

    Article  CAS  PubMed  Google Scholar 

  • Bellizzi D, Cavalcante P, Taverna D, Rose G, Passarino G, Salvioli S, Franceschi C, De Benedictis G (2006) Gene expression of cytokines and cytokine receptors is modulated by the common variability of the mitochondrial DNA in cybrid cell lines. Genes Cells 11:883–891

    Article  CAS  PubMed  Google Scholar 

  • Bellizzi D, Taverna D, D’Aquila P, De Blasi S, De Benedictis G (2009) Mitochondrial DNA variability modulates mRNA and intra-mitochondrial protein levels of HSP60 and HSP75: experimental evidence from cybrid lines. Cell Stress Chaperones 14:265–271

    Article  CAS  PubMed  Google Scholar 

  • Bereiter-Hahn J, Voth M (1994) Dynamics of mitochondria in living cells: shape changes, dislocation, fusion, and fission of mitochondria. Microsc Res Technol 27:198–219

    Article  CAS  Google Scholar 

  • Bertoni-Freddari C, Fattoretti P, Casoli T, Spagna C, Meier-Ruge W, Ulrich J (1993) Morphological plasticity of synaptic mitochondria during aging. Brain Res 628:193–200

    Article  CAS  PubMed  Google Scholar 

  • Bertoni-Freddari C, Fattoretti P, Giorgetti B, Grossi Y, Balietti M, Casoli T, Di Stefano G, Perretta G (2007) Synaptic and mitochondrial morphometry provides structural correlates of successful brain aging. Ann N Y Acad Sci 1097:51–53

    Article  PubMed  Google Scholar 

  • Bjornsson HT, Sigurdsson MI, Fallin MD, Irizarry RA, Aspelund T, Cui H, Yu W, Rongione MA, Ekstrom TJ, Harris TB, Launer LJ, Eiriksdottir G, Leppert MF, Sapienza C, Gudnason V, Feinberg AP (2008) Intra-individual change in DNA methylation over time with familial clustering. JAMA 299:2877–2883

    Article  CAS  PubMed  Google Scholar 

  • Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, Suh H, Sparrow D, Vokonas P, Baccarelli A (2009) Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech Ageing Dev 130:234–239

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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 7:552–560

    Article  CAS  PubMed  Google Scholar 

  • Calvanese V, Lara E, Kahn A, Fraga MF (2009) The role of epigenetics in aging and age-related diseases. Ageing Res Rev 8:268–276

    Article  CAS  PubMed  Google Scholar 

  • Caroppi P, Sinibaldi F, Fiorucci L, Santucci R (2009) Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome C as proapoptotic protein. Curr Med Chem 16:4058–4065

    CAS  PubMed  Google Scholar 

  • Chan DC (2006) Mitochondria: dynamic organelles in disease, aging, and development. Cell 125:1241–1252

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Chan DC (2009) Mitochondrial dynamics—fusion, fission, movement, and mitophagy in neurodegenerative diseases. Hum Mol Genet 18:R169–176

    Article  CAS  PubMed  Google Scholar 

  • Chinnery PF, Johnson MA, Wardell TM, Singh-Kler R, Hayes C, Brown DT, Taylor RW, Bindoff LA, Turnbull DM (2000) The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol 48:188–193

    Article  CAS  PubMed  Google Scholar 

  • Corral-Debrinski M, Shoffner JM, Lott MT, Wallace DC (1992) Association of mitochondrial DNA damage with aging and coronary atherosclerotic heart disease. Mutat Res 275:169–180

    CAS  PubMed  Google Scholar 

  • Cortopassi GA, Shibata D, Soong NW, Arnheim N (1992) A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA 89:7370–7374

    Article  CAS  PubMed  Google Scholar 

  • Cotney J, Wang Z, Shadel GS (2007) Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression. Nucleic Acids Res 35:4042–4054

    Article  CAS  PubMed  Google Scholar 

  • Danielson SR, Wong A, Carelli V, Martinuzzi A, Schapira AH, Cortopassi GA (2002) Cells bearing mutations causing Leber’s hereditary optic neuropathy are sensitized to Fas-Induced apoptosis. J Biol Chem 277:5810–5815

    Article  CAS  PubMed  Google Scholar 

  • Das DK, George A, Liu XK, Rao PS (1989) Detection of hydroxyl radical in the mitochondria of ischemic-reperfused myocardium by trapping with salicylate. Biochem Biophys Res Commun 165:1004–1009

    Article  CAS  PubMed  Google Scholar 

  • De Benedictis G, Rose G, Carrieri G, De Luca M, Falcone E, Passarino G, Bonafe M, Monti D, Baggio G, Bertolini S, Mari D, Mattace R, Franceschi C (1999) Mitochondrial DNA inherited variants are associated with successful aging and longevity in humans. FASEB J 13:1532–1536

    PubMed  Google Scholar 

  • Di Mauro S, Tanji K, Bonilla E, Pallotti F, Schon EA (2002) Mitochondrial abnormalities in muscle and other aging cells: classification, causes, and effects. Muscle Nerve 26:597–607

    Article  CAS  Google Scholar 

  • Dietrich MO, Horvath TL (2010) The role of mitochondrial uncoupling proteins in lifespan. Pflugers Arch 459:269–275

    Article  CAS  PubMed  Google Scholar 

  • Dimauro S (2010) A history of mitochondrial diseases. J Inherit Metab Dis. doi:10.1007/s10545-010-9082-x

  • Dirks A, Leeuwenburgh C (2002) Apoptosis in skeletal muscle with aging. Am J Physiol Regul Integr Comp Physiol 282:R519–R527

    CAS  PubMed  Google Scholar 

  • Drouet M, Lauthier F, Charmes JP, Sauvage P, Ratinaud MH (1999) Age-associated changes in mitochondrial parameters on peripheral human lymphocytes. Exp Gerontol 34:843–852

    Article  CAS  PubMed  Google Scholar 

  • Echtay KS (2007) Mitochondrial uncoupling proteins—what is their physiological role? Free Radic Biol Med 43:1351–1371

    Article  CAS  PubMed  Google Scholar 

  • Edgar D, Shabalina I, Camara Y, Wredenberg A, Calvaruso MA, Nijtmans L, Nedergaard J, Cannon B, Larsson NG, Trifunovic A (2009) Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab 10:131–138

    Article  CAS  PubMed  Google Scholar 

  • Esposito LA, Melov S, Panov A, Cottrell BA, Wallace DC (1999) Mitochondrial disease in mouse results in increased oxidative stress. Proc Natl Acad Sci USA 96:4820–4825

    Article  CAS  PubMed  Google Scholar 

  • Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM (2002) Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet 31:289–294

    Article  CAS  PubMed  Google Scholar 

  • Fannin SW, Lesnefsky EJ, Slabe TJ, Hassan MO, Hoppel CL (1999) Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria. Arch Biochem Biophys 372:399–407

    Article  CAS  PubMed  Google Scholar 

  • Ferrucci L, Giallauria F, Schlessinger D (2008) Mapping the road to resilience: novel math for the study of frailty. Mech Ageing Dev 129:677–679

    Article  PubMed  Google Scholar 

  • Figueiredo PA, Ferreira RM, Appell HJ, Duarte JA (2008) Age-induced morphological, biochemical, and functional alterations in isolated mitochondria from murine skeletal muscle. J Gerontol A Biol Sci Med Sci 63:350–359

    PubMed  Google Scholar 

  • Figueiredo PA, Powers SK, Ferreira RM, Appell HJ, Duarte JA (2009) Aging impairs skeletal muscle mitochondrial bioenergetic function. J Gerontol A Biol Sci Med Sci 64:21–33

    PubMed  Google Scholar 

  • Fish J, Raule N, Attardi G (2004) Discovery of a major D-loop replication origin reveals two modes of human mtDNA synthesis. Science 306:2098–2101

    Article  CAS  PubMed  Google Scholar 

  • Fraga MF, Esteller M (2007) Epigenetics and aging: the targets and the marks. Trends Genet 23:413–418

    Article  CAS  PubMed  Google Scholar 

  • 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 102:10604–10609

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, Salvioli S, Valensin S, De Benedictis G, Di Iorio A, Caruso C, Paolisso G, Monti D (2005) Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 126:351–361

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105

    Article  CAS  PubMed  Google Scholar 

  • Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA, Cardiovascular Health Study Collaborative Research Group (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146–156

    CAS  PubMed  Google Scholar 

  • Fuke C, Shimabukuro M, Petronis A, Sugimoto J, Oda T, Miura K, Miyazaki T, Ogura C, Okazaki Y, Jinno Y (2004) Age related changes in 5-methylcytosine content in human peripheral leukocytes and placentas: an HPLC-based study. Ann Hum Genet 68:196–204

    Article  CAS  PubMed  Google Scholar 

  • Goldberg AD, Allis CD, Bernstein E (2007) Epigenetics: a landscape takes shape. Cell 128:635–638

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Harper ME, Antoniou A, Bevilacqua L, Bezaire V, Monemdjou S (2002) Cellular energy expenditure and the importance of uncoupling. J Anim Sci 80:E90–E97

    Google Scholar 

  • Hepple RT (2009) Why eating less keeps mitochondria working in aged skeletal muscle. Exerc Sport Sci Rev 37:23–28

    Article  PubMed  Google Scholar 

  • Higami Y, Shimokawa I (2000) Apoptosis in the aging process. Cell Tissue Res 301:125–132

    Article  CAS  PubMed  Google Scholar 

  • Hofmann S, Bezold R, Jaksch M, Obermaier-Kusser B, Mertens S, Kaufhold P, Rabl W, Hecker W, Gerbitz K (1997) Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes. Genomics 39:8–18

    Article  CAS  PubMed  Google Scholar 

  • Hudson G, Carelli V, Spruijt L, Gerards M, Mowbray C, Achilli A, Pyle A, Elson J, Howell N, La Morgia C, Valentino ML, Huoponen K, Savontaus ML, Nikoskelainen E, Sadun AA, Salomao SR, Belfort R Jr, Griffiths P, Man PY, de Coo RF, Horvath R, Zeviani M, Smeets HJ, Torroni A, Chinnery PF (2007) Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background. Am J Hum Genet 81:228–233

    Article  CAS  PubMed  Google Scholar 

  • Jendrach M, Pohl S, Vöth M, Kowald A, Hammerstein P, Bereiter-Hahn J (2005) Morpho-dynamic changes of mitochondria during ageing of human endothelial cells. Mech Ageing Dev 126:813–821

    Article  CAS  PubMed  Google Scholar 

  • Jia JJ, Zhang X, Ge CR, Jois M (2009) The polymorphisms of UCP2 and UCP3 genes associated with fat metabolism, obesity and diabetes. Obes Rev 10:519–526

    Article  CAS  PubMed  Google Scholar 

  • Kajstura J, Cheng W, Sarangarajan R, Li P, Li B, Nitahara JA, Chapnick S, Reiss K, Olivetti G, Anversa P (1996) Necrotic and apoptotic myocyte cell death in the aging heart of Fisher 344 rats. Am J Physiol 271:H1215–H1228

    CAS  PubMed  Google Scholar 

  • Kakkar P, Singh BK (2007) Mitochondria: a hub of redox activities and cellular distress control. Mol Cell Biochem 305:235–253

    Article  CAS  PubMed  Google Scholar 

  • Kawakami K, Nakamura A, Ishigami A, Goto S, Takahashi R (2009) Age-related difference of site-specific histone modifications in rat liver. Biogerontology 10:415–421

    Article  CAS  PubMed  Google Scholar 

  • King MP, Attardi G (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246:500–503

    Article  CAS  PubMed  Google Scholar 

  • Kissova I, Deffieu M, Manon S, Camougrand N (2004) Uth1p is involved in the autophagic degradation of mitochondria. J Biol Chem 279:39068–39074

    Article  CAS  PubMed  Google Scholar 

  • Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, Scozzari R, Modiano D, Coppa A, de Knijff P, Feldman M, Cavalli-Sforza LL, Oefner PJ (2006) The role of selection in the evolution of human mitochondrial genomes. Genetics 172:373–387

    Article  CAS  PubMed  Google Scholar 

  • Krauss S, Zhang CY, Lowell BB (2005) The mitochondrial uncoupling-protein homologues. Nat Rev Mol Cell Biol 6:248–261

    Article  CAS  PubMed  Google Scholar 

  • Kroemer G, Reed JC (2000) Mitochondrial control of cell death. Nat Med 6:513–519

    Article  CAS  PubMed  Google Scholar 

  • Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA, Morrow JD, Van Remmen H, Sedivy JM, Yamasoba T, Tanokura M, Weindruch R, Leeuwenburgh C, Prolla TA (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–484

    Article  CAS  PubMed  Google Scholar 

  • Lee CT, Duerre JA (1974) Changes in histone methylase activity of rat brain and liver with ageing. Nature 251:240–242

    Article  CAS  PubMed  Google Scholar 

  • 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 282:22977–22983

    Article  CAS  PubMed  Google Scholar 

  • Lemasters JJ, Theruvath TP, Zhong Z, Nieminen AL (2009) Mitochondrial calcium and the permeability transition in cell death. Biochim Biophys Acta 1787:1395–1401

    Article  CAS  PubMed  Google Scholar 

  • Lennartsson A, Ekwall K (2009) Histone modification patterns and epigenetic codes. Biochim Biophys Acta 1790:863–868

    CAS  PubMed  Google Scholar 

  • Lestienne P, Bataillé N (1994) Mitochondrial DNA alterations and genetic diseases: a review. Biomed Pharmacother 48:199–214

    Article  CAS  PubMed  Google Scholar 

  • Ling C, Poulsen P, Simonsson S, Rönn T, Holmkvist J, Almgren P, Hagert P, Nilsson E, Mabey AG, Nilsson P, Vaag A, Groop L (2007) Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle. J Clin Invest 117:3427–3435

    Article  CAS  PubMed  Google Scholar 

  • Ling C, Del Guerra S, Lupi R, Rönn T, Granhall C, Luthman H, Masiello P, Marchetti P, Groop L, Del Prato S (2008) Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion. Diabetologia 51:615–622

    Article  CAS  PubMed  Google Scholar 

  • Loeb LA, Wallace DC, Martin GM (2005) The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. Proc Natl Acad Sci USA 102:18769–18770

    Article  CAS  PubMed  Google Scholar 

  • López-Lluch G, Irusta PM, Navas P, de Cabo R (2008) Mitochondrial biogenesis and healthy aging. Exp Gerontol 43:813–819

    Article  PubMed  CAS  Google Scholar 

  • Maggio M, Guralnik JM, Longo DL, Ferrucci L (2006) Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci 61:575–584

    PubMed  Google Scholar 

  • Malik S, Sudoyo H, Pramoonjago P, Suryadi H, Sukarna T, Njunting M, Sahiratmadja E, Marzuki S (2002) Nuclear mitochondrial interplay in the modulation of the homopolymeric tract length heteroplasmy in the control (D-loop) region of the mitochondrial DNA. Hum Genet 110:402–411

    Article  CAS  PubMed  Google Scholar 

  • Marzetti E, Anne Lees H, Eva Wohlgemuth S, Leeuwenburgh C (2009) Sarcopenia of aging: underlying cellular mechanisms and protection by calorie restriction. Biofactors 35:28–35

    Article  CAS  PubMed  Google Scholar 

  • Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR, Lithgow GJ (2000) Extension of life-span with superoxide dismutase/catalase mimetics. Science 289:1567–1569

    Article  CAS  PubMed  Google Scholar 

  • Metodiev MD, Lesko N, Park CB, Cámara Y, Shi Y, Wibom R, Hultenby K, Gustafsson CM, Larsson NG (2009) Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab 9:386–397

    Article  CAS  PubMed  Google Scholar 

  • Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G, Attardi G (1999) Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science 286:774–779

    Article  CAS  PubMed  Google Scholar 

  • Molina AJ, Wikstrom JD, Stiles L, Las G, Mohamed H, Elorza A, Walzer G, Twig G, Katz S, Corkey BE, Shirihai OS (2009) Mitochondrial networking protects beta-cells from nutrient-induced apoptosis. Diabetes 58:2303–2315

    Article  CAS  PubMed  Google Scholar 

  • Möpert K, Hajek P, Frank S, Chen C, Kaufmann J, Santel A (2009) Loss of Drp1 function alters OPA1 processing and changes mitochondrial membrane organization. Exp Cell Res 15:2165–2180

    Article  CAS  Google Scholar 

  • Morgan HD, Santos F, Green K, Dean W, Reik W (2005) Epigenetic reprogramming in mammals. Hum Mol Genet 1:R47–58

    Article  CAS  Google Scholar 

  • Naviaux RK (2008) Mitochondrial control of epigenetics. Cancer Biol Ther 7:1191–1193

    Article  CAS  PubMed  Google Scholar 

  • Niemi AK, Hervonen A, Hurme M, Karhunen PJ, Jylhä M, Majamaa K (2003) Mitochondrial DNA polymorphisms associated with longevity in a Finnish population. Hum Genet 112:29–33

    Article  CAS  PubMed  Google Scholar 

  • Nübel T, Ricquier D (2006) Respiration under control of uncoupling proteins: clinical perspective. Horm Res 65:300–310

    Article  PubMed  CAS  Google Scholar 

  • Olivieri A, Achilli A, Pala M, Battaglia V, Fornarino S, Al-Zahery N, Scozzari R, Cruciani F, Behar DM, Dugoujon JM, Coudray C, Santachiara-Benerecetti AS, Semino O, Bandelt HJ, Torroni A (2006) The mtDNA legacy of the Levantine early Upper Palaeolithic in Africa. Science 314:1767–1770

    Article  CAS  PubMed  Google Scholar 

  • Ono T, Isobe K, Nakada K, Hayashi JI (2001) Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria. Nat Genet 28:272–275

    Article  CAS  PubMed  Google Scholar 

  • Ozawa T (1997) Genetic and functional changes in mitochondria associated with aging. Physiol Rev 77:425–464

    CAS  PubMed  Google Scholar 

  • Passarino G, Semino O, Quintana-Murci L, Excoffier L, Hammer M, Santachiara-Benerecetti AS (1998) Different genetic components in the Ethiopian population, identified by mtDNA and Y-chromosome polymorphisms. Am J Hum Genet 62:420–434

    Article  CAS  PubMed  Google Scholar 

  • Perls T, Kunkel LM, Puca AA (2002) The genetics of exceptional human longevity. J Am Geriatr Soc 50:359–368

    Article  PubMed  Google Scholar 

  • Phelouzat MA, Laforge T, Arbogast A, Quadri RA, Boutet S, Proust JJ (1997) Susceptibility to apoptosis of T lymphocytes from elderly human is associated with increased in vivo expression of functional Fas receptors. Mech Ageing Dev 96:35–46

    Article  CAS  PubMed  Google Scholar 

  • Pollack Y, Kasir J, Shemer R, Metzger S, Szyf M (1984) Methylation pattern of mouse mitochondrial DNA. Nucleic Acids Res 12:4811–4824

    Article  CAS  PubMed  Google Scholar 

  • Quintana-Murci L, Semino O, Bandelt HJ, Passarino G, McElreavey K, Santachiara-Benerecetti AS (1999) Genetic evidence of an early exit of Homo sapiens sapiens from Africa through eastern Africa. Nat Genet 23:437–441

    Article  CAS  PubMed  Google Scholar 

  • Richards M, Côrte-Real H, Forster P, Macaulay V, Wilkinson-Herbots H, Demaine A, Papiha S, Hedges R, Bandelt HJ, Sykes B (1996) Paleolithic and neolithic lineages in the European mitochondrial gene pool. Am J Hum Genet 59:185–203

    CAS  PubMed  Google Scholar 

  • Richards M, Macaulay V, Hickey E, Vega E, Sykes B, Guida V, Rengo C, Sellitto D, Cruciani F, Kivisild T, Villems R, Thomas M, Rychkov S, Rychkov O, Rychkov Y, Gölge M, Dimitrov D, Hill E, Bradley D, Romano V, Calì F, Vona G, Demaine A, Papiha S, Triantaphyllidis C, Stefanescu G, Hatina J, Belledi M, Di Rienzo A, Novelletto A, Oppenheim A, Nørby S, Al-Zaheri N, Santachiara-Benerecetti S, Scozzari R, Torroni A, Bandelt HJ (2000) Tracing European founder lineages in the Near Eastern mtDNA pool. Am J Hum Genetics 67:1251–1276

    CAS  Google Scholar 

  • Richardson B (2003) Impact of aging on DNA methylation. Ageing Res Rev 2:245–261

    Article  CAS  PubMed  Google Scholar 

  • Rönn T, Poulsen P, Hansson O, Holmkvist J, Almgren P, Nilsson P, Tuomi T, Isomaa B, Groop L, Vaag A, Ling C (2008) Age influences DNA methylation and gene expression of COX7A1 in human skeletal muscle. Diabetologia 51:1159–1168

    Article  PubMed  CAS  Google Scholar 

  • Rose G, Passarino G, Carrieri G, Altomare K, Greco V, Bertolini S, Bonafè M, Franceschi C, De Benedictis G (2001) Paradoxes in longevity: sequence analysis of mtDNA haplogroup J in centenarians. Eur J Hum Genet 9:701–707

    Article  CAS  PubMed  Google Scholar 

  • Rose G, Passarino G, Franceschi C, De Benedictis G (2002) The variability of the mitochondrial genome in human aging: a key for life and death? Int J Biochem Cell Biol 34:1449–11460

    Article  CAS  PubMed  Google Scholar 

  • Rose G, Passarino G, Scornaienchi V, Romeo G, Dato S, Bellizzi D, Mari V, Feraco E, Maletta R, Bruni A, Franceschi C, De Benedictis G (2007) The mitochondrial DNA control region shows genetically correlated levels of heteroplasmy in leukocytes of centenarians and their offspring. BMC Genomics 8:293

    Article  PubMed  CAS  Google Scholar 

  • Ross OA, McCormack R, Curran MD, Duguid RA, Barnett YA, Rea IM, Middleton D (2001) Mitochondrial DNA polymorphism: its role in longevity of the Irish population. Exp Gerontol 36:1161–1178

    Article  CAS  PubMed  Google Scholar 

  • Salopuro T, Pulkkinen L, Lindström J, Kolehmainen M, Tolppanen AM, Eriksson JG, Valle TT, Aunola S, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Laakso M, Uusitupa M (2009) Variation in the UCP2 and UCP3 genes associates with abdominal obesity and serum lipids: the Finnish Diabetes Prevention Study. BMC Med Genet 10:94

    Article  PubMed  CAS  Google Scholar 

  • Salvioli S, Capri M, Santoro A, Raule N, Sevini F, Lukas S, Lanzarini C, Monti D, Passarino G, Rose G, De Benedictis G, Franceschi C (2008) The impact of mitochondrial DNA on human lifespan: a view from studies on centenarians. Biotechnol J 3:740–749

    Article  CAS  PubMed  Google Scholar 

  • Santoro A, Salvioli S, Raule N, Capri M, Sevini F, Valensin S, Monti D, Bellizzi D, Passarino G, Rose G, De Benedictis G, Franceschi C (2006) Mitochondrial DNA involvement in human longevity. Biochim Biophys Acta 1757:1388–1399

    Article  CAS  PubMed  Google Scholar 

  • Schon EA, Hirano M, Di Mauro S (1994) Mitochondrial encephalomyopathies: clinical and molecular analysis. J Bioenerg Biomembr 26:291–299

    Article  CAS  PubMed  Google Scholar 

  • Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911

    Article  CAS  PubMed  Google Scholar 

  • Shmookler Reis RJ, Goldstein S (1983) Mitochondrial DNA in mortal and immortal human cells. J Biol Chem 258:9078–9085

    CAS  PubMed  Google Scholar 

  • Šimková H (1998) Methylation of mitochondrial DNA in carrot (Daucus carota L.). Plant Cell Rep 17:220–224

    Article  Google Scholar 

  • Smiraglia DJ, Kulawiec M, Bistulfi GL, Gupta SG, Singh KK (2008) A novel role for mitochondria in regulating epigenetic modification in the nucleus. Cancer Biol Ther 7:1182–1190

    Article  CAS  PubMed  Google Scholar 

  • Smits P, Mattijssen S, Morava E, van den Brand M, van den Brandt F, Wijburg F, Pruijn G, Smeitink J, Nijtmans L, Rodenburg R, van den Heuvel L (2010) Functional consequences of mitochondrial tRNA(Trp) and tRNA(Arg) mutations causing combined OXPHOS defects. Eur J Hum Genet 18:324–329

    Article  CAS  PubMed  Google Scholar 

  • Speakman JR, Talbot DA, Selman C, Snart S, McLaren JS, Redman P, Krol E, Jackson DM, Johnson MS, Brand MD (2004) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3:87–95

    Article  CAS  PubMed  Google Scholar 

  • Spinazzola A, Zeviani M (2009) Mitochondrial diseases: a cross-talk between mitochondrial and nuclear genomes. Adv Exp Med Biol 652:69–84

    Article  CAS  PubMed  Google Scholar 

  • Suen DF, Norris KL, Youle RJ (2008) Mitochondrial dynamics and apoptosis. Genes Dev 22:1577–1590

    Article  CAS  PubMed  Google Scholar 

  • Suissa S, Wang Z, Poole J, Wittkopp S, Feder J, Shutt TE, Wallace DC, Shadel GS, Mishmar D (2009) Ancient mtDNA genetic variants modulate mtDNA transcription and replication. PLoS Genet 5:e1000474

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M, Gong JS, Zhang J, Yoneda M, Yagi K (1998) Mitochondrial genotype associated with longevity. Lancet 351:185–186

    Article  CAS  PubMed  Google Scholar 

  • Tanaka M, Gong J, Zhang J, Yamada Y, Borgeld HJ, Yagi K (2000) Mitochondrial genotype associated with longevity and its inhibitory effect on mutagenesis. Mech Ageing Dev 116:65–76

    Article  CAS  PubMed  Google Scholar 

  • Terman A, Gustafsson B, Brunk UT (2007) Autophagy, organelles and ageing. J Pathol 211:134–143

    Article  CAS  PubMed  Google Scholar 

  • Terzioglu M, Larsson NG (2007) Mitochondrial dysfunction in mammalian ageing. Novartis Found Symp 287:197–208

    Article  CAS  PubMed  Google Scholar 

  • Torroni A, Huoponen K, Francalacci P, Petrozzi M, Morelli L, Scozzari R, Obinu D, Savontaus ML, Wallace DC (1996) Classification of European mtDNAs from an analysis of three European populations. Genetics 144:1835–1850

    CAS  PubMed  Google Scholar 

  • Torroni A, Petrozzi M, D’Urbano L, Sellitto D, Zeviani M, Carrara F, Carducci C, Leuzzi V, Carelli V, Barboni P, De Negri A, Scozzari R (1997) Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484. Am J Hum Genet 60:1107–1121

    CAS  PubMed  Google Scholar 

  • Torroni A, Achilli A, Macaulay V, Richards M, Bandelt HJ (2006) Harvesting the fruit of the human mtDNA tree. Trends Genet 22:339–345

    Article  CAS  PubMed  Google Scholar 

  • Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly YM, Gidlöf S, Oldfors A, Wibom R, Törnell J, Jacobs HT, Larsson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429:417–423

    Article  CAS  PubMed  Google Scholar 

  • Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci USA 102:17993–17998

    Article  CAS  PubMed  Google Scholar 

  • Underhill PA, Kivisild T (2007) Use of y chromosome and mitochondrial DNA population structure in tracing human migrations. Annu Rev Genet 41:539–564

    Article  CAS  PubMed  Google Scholar 

  • Vanyushin BF, Kirnos MD (1977) Structure of animal mitochondrial DNA (base composition, pyrimidine clusters, character of methylation). Biochim Biophys Acta Nucl Acids Protein Synth 475:323–336

    Article  CAS  Google Scholar 

  • Vilkki J, Savontaus ML, Kalimo H, Nikoskelainen EK (1989) Mitochondrial DNA polymorphism in Finnish families with Leber’s hereditary optic neuroretinopathy. Hum Genet 82:208–212

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC (2001) Mouse models for mitochondrial disease. Am J Med Genet 106:71–93

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC (2002) Animal models for mitochondrial disease. Methods Mol Biol 197:3–55

    CAS  PubMed  Google Scholar 

  • Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC (2007) Why do we still have a maternally inherited mitochondrial DNA? Insights from evolutionary medicine. Annu Rev Biochem 76:781–821

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC, Fan W (2009) The pathophysiology of mitochondrial disease as modeled in the mouse. Genes Dev 23:1714–1736

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC, Fan W (2010) Energetics, epigenetics, mitochondrial genetics. Mitochondrion 10:12–31

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC, Zheng XX, Lott MT, Shoffner JM, Hodge JA, Kelley RI, Epstein CM, Hopkins LC (1988a) Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 55:601–610

    Article  CAS  PubMed  Google Scholar 

  • Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ 2nd, Nikoskelainen EK (1988b) Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science 242:1427–1430

    Article  CAS  PubMed  Google Scholar 

  • Walston J, Fedarko N, Yang H, Leng S, Beamer B, Espinoza S, Lipton A, Zheng H, Becker K (2008) The physical and biological characterization of a frail mouse model. J Gerontol A Biol Sci Med Sci 63:391–398

    PubMed  Google Scholar 

  • Wang Y, Michikawa Y, Mallidis C, Bai Y, Woodhouse L, Yarasheski KE, Miller CA, Askanas V, Engel WK, Bhasin S, Attardi G (2001) Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication. Proc Natl Acad Sci USA 98:4022–4027

    Article  CAS  PubMed  Google Scholar 

  • Wang SC, Oelze B, Schumacher A (2008) Age-specific epigenetic drift in late-onset Alzheimer’s disease. PLoS One 16:e2698

    Article  CAS  Google Scholar 

  • Wilson VL, Smith RA, Ma S, Cutler RG (1987) Genomic 5-methyldeoxycytidine decreases with age. J Biol Chem 262:9948–9951

    CAS  PubMed  Google Scholar 

  • Wilson FH, Hariri A, Farhi A, Zhao H, Petersen KF, Toka HR, Nelson-Williams C, Raja KM, Kashgarian M, Shulman GI, Scheinman SJ, Lifton RP (2004) A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science 306:1190–1194

    Article  CAS  PubMed  Google Scholar 

  • Wolkow CA, Iser WB (2006) Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan. Ageing Res Rev 5:196–208

    Article  CAS  PubMed  Google Scholar 

  • Zeviani M, Carelli V (2007) Mitochondrial disorders. Curr Opin Neurol 20:564–571

    Article  CAS  PubMed  Google Scholar 

  • Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, Rowland LP (1988) Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 38:1339–1346

    CAS  PubMed  Google Scholar 

  • Zhang J, Asin-Cayuela J, Fish J, Michikawa Y, Bonafe M, Olivieri F, Passarino G, De Benedictis G, Franceschi C, Attardi G (2003) Strikingly higher frequency in centenarians and twins of mtDNA mutation causing remodeling of replication origin in leukocytes. Proc Natl Acad Sci USA 100:1116–1121

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cell Biology, University of Calabria, 87036, Rende, Italy

    Giuseppe Passarino, Giuseppina Rose & Dina Bellizzi

Authors
  1. Giuseppe Passarino
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giuseppina Rose
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dina Bellizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giuseppe Passarino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Passarino, G., Rose, G. & Bellizzi, D. Mitochondrial function, mitochondrial DNA and ageing: a reappraisal. Biogerontology 11, 575–588 (2010). https://doi.org/10.1007/s10522-010-9294-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-010-9294-3

Keywords

Search

Navigation