ExperimentalGerontology

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 the  intron  interferon- y agene   group  pOItalian

Mt CETTee TEE U“Istituto | EE MEPIS» Nazionale « > di] MP EEi Ricovero ¢ re Cura ¢  t dell’Anziano, EMA GEE_ Ancona, | ee ENA EEA, Italy

Received , | June 7 .//,0 ; received i lint 1 revised | form ./ September .//,0 ; accepted 7 .1 September 4 .//,

Abstract

SABA Oe eecardiovascular ¢ r diseases, r eee LILLIES, neurodegeneration, ¢ ONE J OED NN, osteoarthritis < s and ¢ 1 osteoporosis,  , and ¢ | diabetes. " . Thus, i , itc eestcan t &(cid:3) SY ——“——S ew> hypothesized t i that § t genetic variations i sin  1 pro- ¢   EN ENON SE:r anti-inflammatory « y cytokines r s might i t influence s aN EE &> successful z l ageing < x and | 1 longevity. \ 7(cid:3) 5 NN IE> have s Jr’> studied t 1 the ¢ ee> distribution of - f +874T - ae ren> Ai \ interferon-y ( ee OLD J J OI OI    ial i large r > number of 1 “owesf Italian BNE ON ED1 centenarians t eee ee ee ees to evaluate if the two < ) alleles might be differently 1 / represented i lin} ae gp Maa1 people s as Ts PM‘?> selected f soos| for | ee PE EDD DLEr longevity. I ee Oe.DNAs =~\ samples \ s Were ¢ > obtained f 1 from | 11741 t Italian « 1 centenarians ( 8(cid:2);; cae —) years ¢ sold, ,(cid:15). NEE DTwomen | “reeand <. ~~-men) ; ore) and | from | 248 PN BNI NENT 0 OA”/ <60-year-old | oe NEN OT| control ‘beesubjects | 8;/ } women | and ,=(cid:13) men) | matched | for | ee Te- geographical distribution. EM LEO IEEPolymorphisms |  at  +874  were | ~— Jeeidentified | &(cid:21)   a, ee Neeamplification | refractory | EEEmutational FINESsystem | —— EEE eeemethodology.  The +874T z allele \ “Mee eS> was f ae ees found | less f s frequently i y inc 1 centenarian \ me My Me1 women t meee oe1 than i 1 in ¢ nN ODED ENS1 centenarian 1 1 men ¢ ee aLori  1 control \ ph EERE OP OE| women \ 1 whereas 1 sno s reese ye eee) significant differences \ s Were ( > observed i lint 7am"1 the ¢ Sp nD TR> distribution « 1 of t f the t > two é ) alleles t s between 1 1 male ¢ > or f r female «   . Allele { > frequencies i    ee ne Oe1 centenarian eee ee eee on nee eee eee ee eee ee eee ee ee ee ee eee eee eee ies ee ee ee ee se ne ee ee ee eee ee NN NIN IN DS IID IAIN DEI DIODEmen were not found significantly different from male controls. Possession of the + 874A allele, known to be associated with low IFN-  / production, : NIE OI PLL. significantly 1 ON LIincreases | ; the | - possibility 1 to i  ) achieve « - extended | | longevity, : . suggesting 1 that | : the | - pro-inflammatory : / status Fee OE REN OLDIE DI INI NE ODILE DNDN IScharacteristic of ageing may be detrimental f EE DE ANNI NN| for successful ageing. 7 . The ¢ OE ONE> datum that t weeny?tthe a J? ““oore™> allele was s  PERE MARA MR EEs significantly i IDy increased i a Oe1in female but not 1 male « PEN ME OEE OO- centenarians :   to | ) strengthen 1 the i idea | \ that | “ons: *t gender | ‘may | &(cid:3)   | major 7 variable 1 in | “rethe | NN LIES: biology | of 1 the ; - ageing |   However, , the |   t data < 1 add « ae EO| another | o_Or piece « > of « eeef evidence t oe> tot ) the ¢ ee EEE> complex | ~~ —o—s: puzzle « en”> of § f genetic <   EE III IES FEE| environmental { ——— Soe| factors i  moe’ Powes involved i  lin controlling 1 maw Pes life s ree> span ¢ 1 expectancy i yint nes pea”1 humans. 7  . Thus, s , studies ¢ son ¢ eet1 cytokine § paws pe> gene | CEN IE Ew> polymorphisms 1 s may | y promise t toi ) individuate < >a 1 complex ee ee ee eee ee eee ee ene eee eee ee ne ee ee eee ee eee eee oe ee oe ese ee ene i ee eee ee ene ee NN ON NEED TEnetwork of trans-interactive genes able to influence the type and strength of responses to environmental stressors and as a final result, thereby « ‘ conditioning i ONE ENy individual | | life ¢ > expectancy.  .//. ren eee) Elsevier ‘oem esScience | oer> Inc. : .Allt | rights 1 s reserved.

Keywords: | : Interferon-y; | ; Longevity; 1 ; Inflammation; (  ; Centenarians; | , Immunogenetics

  , Introduction

Human longevity seems to &(cid:3) directly correlated with OE IIISoptimal oer eeefunctioning of the ee NEEimmune system,

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been eereported that the ,. !(cid:1) aa ANSrepeat NOI DU IN ILEmicrosatellite allele ; “orat t t the { > first 1 t intron ¢ . of t F the | ee» IFN-y § pen ae/ gene i > is < ; associated with  higher level of in vitro * F o~wescytokine production (Pravica | “oOet i cal. ,;;;:5 More ov <Irecently | the |   group weavereported an. Reng AA A feabsolute | fe ave heecorrelation ONE MIIbetween the ,. !(cid:1) CPrepeat ; t allele ; > and t | the | > presence « > of t F the ”   ‘allele < at é tan 9> o<Ppeelocated at | the “ee+874 | Peeposition | (+8747 -  (cid:1): } from | | the translation : | Start : t site « pees NO- coinciding ' , with ¢ a] eR| putative | 9’(cid:26)(cid:2)$ binding : site | that 1 | may | &(cid:3) OREO ED NN EARES- important | me |‘int | the : induction « | of EDIE OOD OSconstitutively high “J VeaIFN-y | EE EEEproduction (Pravica | et. al., .///:5 7(cid:3) mw ONE: have § fee ae: studied 1 og PO| the « eee eee NE- distribution « of +874T -   NB ONS_IFN-y | ' polymorphisms | in: a large 1 - number | of | * Italian aN GE RP « YScentenarians to. eeevaluate if the “ONtwo alleles might &(cid:3) differently 1 represented | | in | | people : - selected | | for | A ee‘longev- ity.