(%4+0%%3%B(+BC 0 see | > front 1 t matter  ’((+ | Elsevier r Science | > Inc. 4 . All | rights 1 s reserved. PII: ?(%4+0%%3%<(+>(((;*0:

 _ Introduction

process | (Papa | and Skulachev, +;;,) a ee eeBrierley | et. al., +;;,) > ErLee. and Wei, +;;,) oemMiquel, +;;:) eee Ne epeeBrand, ’((() Kowald aeand ey NOKirkwood, ’((() aaMeloy, ’((() =m ree mRustin aaet al., ’(((>(cid:28) ei eeOxygen eeefree —a aradicals, usually referred to “> <as ae ANEreactive wes ts eeoxygen species <(cid:29)(cid:26)?>(cid:30) 7 <-"‘"are MMSthe SIOmajor : * source | of | —————oxidative | meee ESdamage | - within | the « cell : | and | | lie | tO IEat | the | Ye Peeheart | of | eo““one | aIof | * the 1 / most Ae eeeprominent ; and | | plausible | ~~ eE*theories | EEE INEpostulated, | the | free | radical | theory | of | ageing | (Beckman and , | Ames, +;;:) Cadenas < sand | eee| Davies, ’((() owen; Sastre « et tal., 7 ’(((>(cid:28) — I”_ The 1 So> main s ee em1 SOUrCe ¢ > of | FROS within | tntthe | cell | is | the | aerobic “ree eemetabolic | ee eee/ pathway sw ws eee «located eaewithin | the mitochondrion. | The ROS produced | cause | cumulative eadamage to. cee yoncellular | constituents, DNA, RNA, proteins and | ~A Pree| lipids, 1 that i t is | ; believed t | to1 y result i in < Se aN| ageing ; rand ¢ | eventual « | death. * _ The 1 ae NED ARAN ES pee> mitochondrial | | DNA oe Eeegenome ey EE EE(mtDNA). is. al covalently | eee oeclosed. TOOcircular. ‘ double-stranded | genome |   +3(cid:30)%3;   and | the « “= \eneanan NA ATcomplete | aissequence © was | ye; published | | in +;:+ (Anderson | et i “—— &*val., +;:+>(cid:28) The | Me OE/ mtDNA genome ~~ eeeencodes oTfor ’’ eee ietRNAs, ’ tRNAs and +4 wen NEE OSpolypeptides and it casis. Fe DEN LENEestimated that oemtDNA t . undergoes 1 ; mutations « “eassat: %A+( ) times f 3 faster t os PMr than 1 JI PNP: nuclear | r DNA ( (aDNA).’ . There ¢ > are < > at least t t two | eee ES) factors i ; implicated i lin] | promoting 1 r this | s high 1 1 rate > of 1 F mutation; ( <(cid:2)> nee NA)) there < Aye as> are | >no | ) histone proteins to eee ETDprotect  “mtDN A Preeand, <(cid:2)(cid:2)> a =there    aonly  very  inefficient repair mechanism eeeagainst | wees reredamaged | | DNA.

DNA is located in an area termed the “oOo eeecontrol 7 Spreeregion. The wee eMcontrol region is the variable region of the human mtDNA genome i —and is the location | of "the loop Ns  oooeeee(D-loop).  number of features Oe EEexhibited by the mtDNA EN NE OTE(polymorphic aN Fematernal “Pstmode | of inheritance, lack | of | EE II IID IErecombination | and eNOSrelatively | oN eeesmall a pee meeegenome) led to its analysis by hE ERED NAG ERANmolecular approaches being widely EN NEY ODexploited in < Cottrell et “ee 2al., ’(((> and ee eeeanthropological ISstudies, EE ESEproviding  clearer ree oninsight —————ehuman | os ey etevolution, | MN I AMorigins | and | hE EEpatterns mao migration | “pee_(Torroni | et | cal., +;;’) EEE ED_Torroni | et. +;;*) Torroni eeeet nn =)al., +;;3) ~~ peeIngman et aal., ’(((>(cid:28) AAUIt is now ““ “enedwell DA AE DE NILEestablished that “any ae,numerous | ; mtDNA : BROOD EA AMD. Sequence ° RAAT RREE MR RRR- variants/haplotypes, « Ms aedefined | | by 1 restriction | | enzyme | that | exist - within | | the | oe eR- European | pT“aucasian | os I PMs eee| population can | 5be   re NEM JOO| within | nine | mtDNA | . haplogroups; |] 9(cid:30) I. &(cid:30) E(cid:30) .(cid:30) D(cid:30) I(cid:30) G(cid:30) “eeeand) J(cid:30) , differentiated « lont \ the | basis « 3 of i EN EE EE EEE EEEpolymorphisms | SMM RAD A; (Torroni «  “cal., +;;3>(cid:28)

associated | with | longevity 1 in| ) humans. | De] > Benedictis ; sand « AN NE| colleagues 1 we PO eee: reported las | statistically significant i BONEN ELIE{ increase ONT>in t cred1 the { EEN IEEE INE- frequency ¢ / of t f the | - broad | & IDE NEIL IIASA| haplogroup, ¢ “SoM eb, defined t iby t / the | ee OE> polymorphic ENrestriction s | site +3(3%(cid:21)(cid:30) int “Tee| male « EN YE IN OIE> centenarians | ; from 1 are\ the 1 avonsnorth “ro™of | Italy « eM MF a Pecompared 1 | to yee Pee. younger males from   sameao 9 enregion  Benedictis et   +;;;>(cid:28)  The J weeother eetwo OE FE ONindependent studies identified ee ES Eeeincreases in anthe frequencies of meg nAthe AFR A ION NINESmitochondrial NNpolymorphisms at position | (cid:17)(cid:3)%+,: < to. (cid:14)> )in. | Japanese | es einecentenarians | , (Tanaka « et al., +;;:> dg) and 1 (cid:17)(cid:3);(%% <@ to. (cid:14)> )in) | French | a eam eae| centenarians | “eee; (Ivanova | et cal., +;;:>(cid:28)

evity  Feerand | ee POO| promote : : successful ¢  | ageing | WAS | ; assessed 1 [int “Pe\ the | rspresent :  t study. | A. For t   OD; analysis  ’3*4 bp “eeesection <(cid:17)(cid:3)+4;(:0+3%%+> o *of the mtDNA oe Ne |was brewstargeted and subjected to of eeehigh- aN MEdensity ree NSrestriction SEEN EEenzyme ae PManalysis as outlined SERENE EE EDpreviously ——~—o~ re(Torroni et i Dateal., +;;*>(cid:28) AeThis NOtregion | itof | ‘the 1 /mtDNA | “JeeWas | EEE J OIEselected | | for | a iin| number | rnof 1 or eee DONreasons. | yee eeFirstly, it. me RRRcontained | fe ana| part | of

)*+* . Ross ¢ yet ¢ tal. / , / Experimental ( | Gerontology - /0 123345 4404644(cid:30)7