theESR1PvuIIpolymorphismseemstohaveagreaterim- allelecreatesabindingsiteforthemybfamilyoftranscrip- estrogen action, although the real impact of ESR1 showingthatgenesinvolvedinestrogensynthesisandac- surprisingasestrogeninfluencesvariousdifferentphysio- logical processes and is involved in the of many diseases of advanced age which, in turn, influencethelifespanofbothmenandwomen.Inagree- mentwiththisobservation,ESR1andCYP19geneticpoly- morphisms in relation to cardiovascular disease, Alzheimer’s disease (5,18–23,25–27) have been

Funding

ThisworkwassupportedbytheItalianNationalResearchCounciland LaSapienzaUniversitygrants.

Christense

,Johnso

E,Vaupe

W.Thequestforgeneticdetermi- nantsofhumanlongevity:challengesandinsights.Nat Rev

;

:

–

contributiontobiologicalaging:th

ramingha

tudy.J Gerontol A Biol Sci Med Sci.

;

:

–

Karasi

,Demissi

,Cupple

A,Kie

P.Disentanglingthege- the use of survival measures. J Gerontol A Biol Sci Med

;

:

–

Consortium.J Gerontol A Biol Sci Med Sci.

;

:

–

Dero

J,Korac

S.Estrogenreceptorsandhumandisease.J Clin Invest.

;

:

–

Garcia-Segur

M,Azcoiti

,Do

arlo

L.Neuroprotectionbyes- tradiol.Prog Neurobiol.

;

:

–

cardiovascularsystem.N Engl J Med.

;

:

–

ceptorgenes:effectsonmaleaging.Exp

thesexes.Proc Natl Acad Sci U S A.

;

:

–

mortalityselection.Am J Hum Biol.

;

:

–

ductivesuccess.Nature.

;

:

–

aristocraticandrura

innishfamiliesinthe

sand

s.Proc Soc Lond B Biol Sci.

;

:

–

Ageing Res Rev.

;

:

–

onhumanfertility.Biogerontology.

;

:

–

successful ageing: genetic background of male centenarians protective against coronary heart disease. J Med Genet.

–

Huizinga TW. Optimizing human fertility and survival. Nat

;

:

rolesandgenomicorganizationofpromoters.J Steroid Biochem Biol.

;

:

–

er’sdiseaseinwomen.Dement Geriatr Cogn

easerisk.Dement Geriatr Cogn Disord.

;

:

–

repeat influences aromatase activity and estrogen levels in men:effectsonbonemetabolism.J Clin Endocr

–

Hum Mol Genet.

;

:

–

er’sdisease.J Med Genet.

;

:e

–

twee

Ralphaan

Rbeta.Mol Interv.

;

:

–

ease.Biochem Biophys Res Commun.

;

:

–

tions.Dement Geriatr Cogn Disord.

;

:

–

Iso

,J

,Urakam

,Adach

,Nakashim

Geneticassociation ofestrogenreceptorgenepolymorphismswit

lzheimer’sdisease. Alzheimer Res.

;

:

–

Corb

M,Ulizz

,Piomb

,Martinez-Labarg

,D

tefan

F, Scacch

Estrogenreceptoralpha(ESR

)polymorphismsandfertil- ityinpopulationswithdifferentreproductivepatterns.Mol Hum Re- prod.

;

:

–

Crest

,Gregori

Ildisegnodellostudi

ONCILE.Riv Antropol.

;

:

–

Mille

A,Dyke

D,Polesk

F.Asimplesaltingoutprocedurefor extracting DNA from human nucleated cells. Nucleic Acids Res.

;

:

Herringto

M,Howar

D,Brosniha

,etal.Commonestrogen receptorpolymorphismaugmentseffectso

RTo

-selectinbutnot C-reactiveprotein.Circulation.

;

:

–

Herringto

M,Howar

D,Hawkin

A,etal.Estrogen-receptor polymorphismsandeffectsofestrogenreplacementonhigh-density lipoproteincholesterolinwomenwithcoronarydisease.N Engl J Med.

;

:

–

Maruyam

,Toj

,Harringto

R,etal.Lackofanassociationof estrogenreceptoralphagenepolymorphismsandtranscriptionalactiv- itywit

lzheimerdisease.Arch Neurol.

;

:

–

Yaic

,Dupon

D,Cavene

R,Par

F.Analysisofth

v

Ire- strictionfragmentlengthpolymorphismandexonstructureofthees- trogenreceptorgeneinbreastcancerandperipheralblood.Cancer Res.

;

:

–

Haiman CA, Dossus L, Setiawa

W, et al. Genetic variation at the CYP

A

locus predicts circulating estrogen levels but not breastcancerriskinpostmenopausalwomen.Cancer Res.

;

:

–

Petr

J,On

K,Michelmor

F,etal.Associationofaromatase (CYP

)genevariationwithfeaturesofhyperandrogenismintwo populationsofyoungwomen.Hum Reprod.

;

:

–

Terwillige

,Ot

Handbook for Human Genetic Linkage.Balti- more,MD:Joh

opkin

niversit

ress;

Capr

,Salviol

,Mont

,etal.Humanlongevitywithinanevolu- tionaryperspective:thepeculiarparadigmofapost-reproductivege- netics.Exp Gerontol.

;

:

–

D

ang

,Dat

,Bellizz

,etal.Anovelsamplingdesigntoex- ploregene-longevityassociations:th

CHAstudy.Eur J Hum Genet.

;

:

–

Kjaergaar

D,Ellervi

,Tybjaerg-Hanse

,etal.Estrogenrecep- toralphapolymorphismandriskofcardiovasculardisease,cancer, andhipfracture:cross-sectional,cohort,andcase-controlstudiesand ameta-analysis.Circulation.

;

:

–

Vin

,Sastr

,PallardòFV,Gambin

,Borrà

Modulationof longevity-associated genes by estrogens or phytoestrogens. Biol Chem.

;

:

–

Sundarraja

,Lia

,Ro

C,N

C.Associationofoestrogenre- ceptorgenepolymorphismswithoutcomeofovarianstimulationin patientsundergoin

VF.Mol Hum Reprod.

;

:

–

Kukuviti

,Georgio

,Boub

,etal.Associationofoestrogenre- ceptoralphapolymorphismsandandrogenrecepto

AGtrinucleo- tiderepeatswithmaleinfertility:astudyin

Greekinfertilemen. Int J Androl.

;

:

–

from http://biomedgerontology.oxfordjournals.org/ at New York Medical College on November 16, 2014