:

–

Franceschi C, Motta L, Valensin S and the Italian Multicenter on Centenarians (

b) Do men and women follow different trajectories to reach extreme longevity? Aging Clin Exp Res

–

Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca Ottaviani E and De Benedictis G (

c) Inflamm-aging: evolutionary perspective on immunosenescence. Ann N Y Acad Sci USA

:

–

Garasto S, Rose G, Derango F, Berardelli M, Corsonello A, Feraco E, Mari V, Maletta R, Bruni A, Franceschi C, Carotenuto L and De Benedictis G (

) The study of APOA,APOC

and variability in healthy ageing people reveals another paradox the oldest old subjects. Ann Hum Genet

:

–

Gutsmann-Conrad A, Heydari AR, You S and Richardson A The expression of heat shock protein

decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Exp Cell Res

:

–

Ivanova R, Fhenon N, Lepage V, Charron D, Vicaut E Schachter F (

) HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity. Hum Mol Genet

:

–

On the other hand, it is intriguing to note that HSF- 1 is under positive regulation by estrogen hormones (Yang et al. 1995; Knowlton and Sun 2001), and this is in line with the different effects of (A/C)−110 alleles in the two genders. It is worth noticing, however, that a variety of genes affecting longevity in a sex-specific way have been reported, both for humans (Ivanova et al. 1998; Tan et al. 2001; De Luca et al. 2001; Bonafè et al. 2001; Lio et al. 2002) and model organisms (Jackson et al. 2002; Leips and Mackay 2002).

Since the present study is a cross-sectional one, mortality of genotypes may depend on the birth year of the cohort for oldest-old people (De Benedictis et al. 2001). If this were the case, the (A/C)−110 poly- morphism may affect survival in historical-specific environments, rather than longevity. In any case, the study, carried out in a well defined and homogen- eous population, has shown that the allele (A)−110 of the HSP70-1 gene, which is a strong candidate for affecting life span on the basis of studies in model organisms, is unfavorable to longevity in women.

physiology. Annu Rev Physiol

:

–

Franceschi C, Valensin S, Bonafe M, Paolisso G, Yashin AI, Monti D and De Benedictis G (

a) The network and the remodeling theories of aging: historical background and new perspective. Exp Gerontol

:

–

Franceschi C, Motta L, Valensin S and the Italian Multicenter Study on Centenarians (

b) Do men and women follow different trajectories to reach extreme longevity? Aging Clin Exp Res

:

–

Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E and De Benedictis G (

c) Inflamm-aging: an evolutionary perspective on immunosenescence. Ann N Y Acad Sci USA

:

–

Garasto S, Rose G, Derango F, Berardelli M, Corsonello A, Feraco E, Mari V, Maletta R, Bruni A, Franceschi C, Carotenuto L and De Benedictis G (

) The study of APOA,APOC

and APOA

variability in healthy ageing people reveals another paradox in the oldest old subjects. Ann Hum Genet

:

–

Gutsmann-Conrad A, Heydari AR, You S and Richardson A (

) The expression of heat shock protein

decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Exp Cell Res

:

–

Ivanova R, Fhenon N, Lepage V, Charron D, Vicaut E and Schachter F (

) HLA-DR alleles display sex-dependent effects on survival and discriminate between individual and familial longevity. Hum Mol Genet

:

–

Jackson AU, Galecki AT, Burke DT and Miller RA (

) Mouse loci associated with life span exhibit sex-specific and epistatic effects. J Gerontol A Biol Sci Med Sci

: B

–B

Knowlton AA and Sun L (

) Heat-shock factor-

, steroid hormones, and regulation of heat-shock protein expression in the heart. Am J Physiol Heart Circ Physiol

: H

–

Kregel KC (

) Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J Appl Physiol

:

–

Acknowledgments

This work is funded by the EU-ECHA project ‘European Challenge for Healthy Aging’ (no.: QLRT- 2001-00128, Call Identifier: QOL-2001-3. http:// biologia.unical.it/echa), by the Italian Ministry of Health (IRCCS 2000-2002, Marcatori genetici e biologici di invecchiamento normale e patologico), and by the Italian National Research Center on Aging (INRCA, Ancona & Cosenza, Italy).

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