(cid:17)1 Lio ¢ ) et ¢ tal. / 7 / Experimental ( | Gerontology - $5 : ## ;

might not allow the identification of significant DEE Ee ENdifferences, these data seem to suggest that the genetic —_—S— rearcomponent of the ee EEE EOSlongevity SNe EN NEachievement o“tef™"*may &(cid:3) Ne eeeimportant for women eo NStoo. mae SNeHowever, it has to | &(cid:3) NEremembered that the | expression of or“the 2,“ eeeIFN-y gene | ) may | &(cid:3)   to ) direct | “Pees| hormonal « | control. | In: 1 a oe ODtransient « J VN”| expression | assay, | the : > SEX § steroid | 17B-estra- diol | was | rps; shown | EEE EEE ID| markedly to. increase | the | Co ie heeactivity. of the | /IFN-¥ | / promoter |   ee| lymphoid « | cells | ; that « ON NEE YO/ expressed the “aes Gg peeappropriate nn a |hormone ree eeereceptor. This ~ss pieeffect 1S Bi PPmediated &(cid:21) sequences in the Mmplur. 2AM5/-flanking region | of the gene. eeeHormonal regulation of IIRthis of Yeon Nspleiotropic _™ Execytokine has been aes Soesuggested to EINEaccount in —"part “renfor al ithe | ability | of | NEE OEEestrogens >=“to | potentiate many © pees *types. of I ND IDI IID ILIA JD J EOSimmune responses, and for the disproportionate suscept- ibility of ee eeensewomen to ee NN IIIimmune-inflammatory “endiseases 8’(cid:12)? et é tal., ,;;,0 , Verthelyi « | and | | Klinman, ‘ .///:5 . Thus, eoit] has 1 to | &(cid:3) eee» taken i 2 oe| into ¢ NE YE OO) account t t that | | gene | ey NDvariants 1 saa; repre- senting ¢  1 genetic < > advantage f > for « BEM” Er one | om" Te> gender 1 r might 1 t not t &(cid:3) NEEDED IED ES SEautomatically | relevant | eofor | the a &other ON eee- gender 1 oS“int — ein| terms « of successful « wdLor t J EE IIEr unsuccessful ; | ageing.

might | have : ao peefunctional | consequences | nefor | Sm Atranscription of t a —F the | » human | | IFN-y § / gene. ee eee. Therefore, 1 the’  to, eedyA] “>_—eoO. poly- morphism | | might } Ys fF owes| directly | influence 1 oo Sanethe | level « | of | TFN-y NE OE OEEproduction BOE ER LE NEassociated ‘Joowith the !(cid:1) ae EE EEEmicrosatellite eeemarker | (Pravica | et i val., ’ .///:5

Soactivity ‘oooreflected &(cid:21) increased circulating levels weof DOEpro-inflammatory Se ENOcytokines and acute moO OUphase proteins ee LD(Franceschi et “yO .///(cid:24)0 ENE EERIEBruunsgaard peteet al., .//,:5 re A aeSystemic vane MS Ree aconsequences Se O——include ee = __™pattern of eee Pechanges  MFattributed to. eechronic NN EDI REinflammatory | reneediseases or EOfrailty (Ershler and Keller, .///:5 DOLL J IIL LILLE DEEpidemiological “aestudies ee ONsuggest 1 that t chronic | To NNN- low-grade 1 EE DE EEE- inflammation i in | ageing Moosepromotes an | EE IED INE IIIS OE_ atherogenic | o“:,|_Kprofile | and | | is) related | ne =)to: — a =) age- Pee eeassociated i ON| inflammatory « ~ pee; diseases < s and ¢ 1 enhanced 1 so “ON{ mortal- ity 1 risk | - (Harris « et i cal., ,;;;0 - Bruunsgaard | | et : tal., ‘ .//,:5 ON ED IID NIE OI I A AY IAIN NDL ES IES EDILI NI NAR EIA QJ ANIL IOAccordingly, polymorphic alleles of inflammatory cyto- kines, | &(cid:21) Ory PN Peedetermining eee ee- changes | in « | cytokine | eee PO TON- production, play ao MSan asimportant “me weesrole in oN MDage-related ne IDinflammatory rey see 8diseases, (cid:10)5(cid:3)5 in ROR EDEN IEE EESunsuccessful =~ ee eeageing 8$(cid:23)(cid:12)4(cid:24)6 et meal., .///0 — aeweeeeGrimaldi et al., .///0 onaHobson eseand Ralston, .//,0 McCusker | et. cal, .//,:5 Moreover, it has been recently 1 / reported t l that t =ot the 1 ME Fe aaa> magnitude « > of t F the : eae eee eee es> spontaneous NODrelease ¢ ‘J> of | —————eeorerf IFN-y : yand t ee EN INE| tumour 1 COr necrosis f MERE Oes factor-a f ‘from ] 9N cells i sin, ee SN eee. Alzheimer « r disease | patients « : correlate 1 - negatively with the decrease of “the cc—Ee————e—o~—score of cognitive “oefunction 8 Solerte « et tal., .///:5

evidence | to | ONDE) the « rep Ma peescomplex | puzzle « of genetic ; os beand « | envir- onmental factors eaeinvolved in ce Eeecontrol of life span expectancy i in| 1 humans. | Studies « 5 On ¢ 1 cytokine | > gene | » poly- em Femorphisms may promise to eee Ntindividuate “oOo ae Pescomplex ee eenetwork of EE EO EEEtrans-interactive genes able to _ ~~ bPoeinfluence the type and strength of ms oe"responses to. - environmental me SINstressors ¢ and ; | as j a! “oe. final | eae P”| result, « conditioning 1 - individual life - expectancy.

“aenegative | outcome | for. subjects” wee ONwith a] BOE EES_ pro-inflamma- “Noetory | profile, i ity | makes | os, sense 1 that 1 the | EE IES: possession of 1 “the ae y es+874A Bane BM AMallele, known to &(cid:3) & hi peesassociated with low IFN-y | f GRAN NENG AMS/ production i is | ; significantly | increased | Lin | cente- anaes OT RSnarians. These data LISstrengthen the suggestion that pro-inflammatory status EERE REE EODcharacteristics of ageing reemay &(cid:3) EDI IODIAEED J OURANdetrimental for successful wee SEESageing, ye OOand concomitantly suggests that  tight “oeeeecontrol oof the LILI DELILEinflammatory Moo.status may neecontribute to survival of extreme | — Jages.

Acknowledgements