<(cid:12) the —ooeer—eeeeeewhole, *(cid:21)(cid:11)" “apesworms to "(cid:17)""(cid:17)(cid:10)(cid:5)& the | my aegenes i nsinvolved meee 8in ae Snutritional/metabolic NAAR RAScontrol | hwand | yaaiaws 4.stress | RANE NMAresponse » REAR BADRAEErepresent | RAALAEEan AO BRAIN Btintriguing | VA Beeinterplay. (cid:11)* RRR RINE ENEMIESconsiderable : aieinterest Maafor longevity ( CO EN OEE' (Franceschi « i et i (cid:17)(cid:10)!& (cid:30)000(cid:17)7! In] OE IID IES1 humans, i in | oO Te ee| particular, 1 eo_ three : > such | | genes % are | » located in | “owtthe « ee ENE- chromosomal : soe GODregion —e—v—e11p15 ! ? Tyrosine | EE IEE Hydroxylase | 6(cid:20)(cid:22)& (cid:26)$)? (cid:31)(cid:31)3@(cid:31)(cid:30)7& Insulin 6(cid:24):(cid:1)& (cid:26)$)? (cid:31)(cid:31)3/D37& i — i, Insulin ¢ Sap AN1. Growth |] ef yee1 Factor 7  me) (IGF2, (cid:26)$)? (cid:31)(cid:31)3//(cid:31)7! . THe RR AE TD[ encodes t prs tyrosine ~—_E—————ehydroxylase, the EE AONE ASrate-limiting enzyme in wn et \-the es — oosynthesis (cid:11)* AN ENEcatecholamines, eeeamino acid- ae ONEderived yas er amolecules a =produced o™by is JOthe DON IED EINE ATOsympathetic nervous system in “nen ghTesponse to stress, which act both rEas eeehormones fe Ee eee(adrenaline) and NN NY OOOneurotransmitters ae(dopamine and “eeenor- adrenaline). | INS | - encodes a eee een ne| one-chain | ee PO A| precursor, | , proinsulin, \ . which | eeeMLIS « Le Pee; converted | | to i y insulin by pe ALE EIN Feenzymatic « : cleavage. 1 > . complex 1 eee PE OEDrelationship « "9 pees) exists | EOD NN AM; between i | insulin ¢ and « | catecholamine OF NO FOOregulation ( | (Natali ¢ arei et ¢ (cid:17)(cid:10)!& (cid:31)3327! reso_IGF2 | . encodes i ap Ne ee; insulin-like ; - growth | | factor | “TI, also | ) known : 1 as NE DEE NANsomatomedin . >& as “vm eeeeg ne| single « Aare» chain | | polypeptide, ' , which : | shares a —> an < | amino ; y acid ; ———ooiT—oroem| sequence | : homol- ogy | (cid:11)* “about « DAF “eeewith i EOE| insulin.

Sy MNThe | > genetic 1 - marker | (cid:22)E#(cid:20)(cid:22)<(cid:31)& a 6(cid:20)>.(cid:20)7 , polymorphism | . which | lies i ; inside ’ TH i [ intron   NN ELLIS(Polymeropoulos | et. (cid:17)(cid:10)!& (cid:31)33(cid:31)7 ameand acts |  nran | wee Fe eeeenhancer transcription | element in vitro er a(Meloni | et | (cid:17)(cid:10)!& (cid:31)3327& a ierevealed | BF ELEN LENE EOE| association between |    locus |  and  | human  longevity 6$(cid:2) Veen NeBenedictis « set i (cid:17)(cid:10)!& (cid:31)3327! )(cid:16) ‘recoding | ; HUMTHOI ; alleles ; sas | ; Short | 6(cid:1)7 ) and | “ee ENS| Long ( 6%7 ayealleles (less 1 s than § 2 “seep nwrepeats aaNetsand § 2 — 2 ererepeats 5 OF I oTr more, 1 , respectively), « a clear : NF LEI IAI ESDr sex-dependent DEt association Yew seats’between | NO OS. HUMTHO! ° ee EN eeevariability « rand | nee ye| long | , life « pe ED FOO- expectancy | | was ¢ = OE; observed: | %% , homozygotes were I rarest i Lin « | centenarian | “ome yomales, | but 1 Not i —in | rae Spee| females \ ee; with | Pp owe| respect 1 | to § ) SCX | matched « AMY ONO| controls. Thereafter,   relative-risk  approach confirmed    EEE STassociation between   locus  and longevity :  | showed | os PP| specific | peeeffects : , sustained | | by | single - HUMTHO1 | alleles | (Tan et (cid:17)(cid:10)!& (cid:30)00(cid:31)7! ay oeThe | aim (cid:11)* “the | Speen ™present research was to CF EEOcontinue the | exploration | (cid:11)* ea"the l1p1s ! ee En fe Awchromosomal - region - neein| reweeees *| human longevity, | by. analyzing INS | espand _IGF2> variability “rr:in the

Table |  

INS-FokI-RFLP genotypic and allelic counts and frequencies 6(cid:29)(cid:21)(cid:2);7 in (cid:30)0(cid:23)A0 year old subjects and in   >B9 oe ye> indicates « ; absence/presence (cid:11)* f FokI 1 ee eee[ restriction s we1 site

(cid:30)0(cid:23)A0  ) year ¢  r old s | subjects Centenarians Males Females  Males Females Count  Freq Count  Freq Count  Freq Count  Freq Genotype >> 2 0!A(cid:31)D 3@ 0!A0(cid:31) / 0!A/@ 3/ 0!@// >9 /(cid:30) 0!(cid:30)@3 /A 0!(cid:30)A0 (cid:31)A 0!(cid:30)/@ D2 0!/(cid:30)A 99  0!(cid:31)A D 0!(cid:30)3  0!(cid:30)2 @ 0!D(cid:31) Allele > 202 0!2D3 229 0!2/@ 123 0!2 D (cid:30)/D 0!A3@ 9 /@ 0!(cid:31) S1 D 0!(cid:31)@D 21 0!(cid:31)D@ @0 0!(cid:30)0D

: sample « (cid:11)* healthy « centenarians : already : studied | for’ ‘TH ' | variability. | Fig.  shows | me ee eee> positions ¢ (cid:11)* eedF the *   (cid:24):(cid:1)&  , IGF2 | - loci « weiont | the   ! ) region ‘ . and « (cid:11)* .* *S*the 1 > ees> markers t | the | ~ Eee- analysis.

  , Materials ; ; and | | methods

$,2, Samples