The sample was recruited in 2000 for the multidisciplinary LONCILE (Longevity of Cilento) study on the anthropological and biological characteristics of the elderly population of the Cilento area in the district of Salerno, southern Italy. It consisted of 277 unrelated individuals (43.7% males) born between 1900 and 1930 (mean age, 82.9±5.7 years standard deviation [SD]), enrolled without selection criteria, except age (> 70 years) and birthplace. Mortality data on 267 subjects were collected in 2009. In 2000, 14.5% were aged 90 years old or older. During the 9-year follow-up period, the mortality rate was 62.5% (51.5 % men); 55.1% of the subjects died before reaching the age of 90 years. As the mean life expectancy in this Italian geographic area for subjects aged 83 years old is 7 years for women and 6 years for men (ISTAT, http://demo.istat.it/unitav/index.html/), we defined as long-lived those subjects who survived to over age 90 years (≥90 years). The sample of the long-lived (n=114) comprised subjects aged 90 years or older in 2000 (regardless of whether the participants were still living or not). Table 1 reports the distribution of the FSHR 680 genotypes in the long-lived and the controls of both sexes. A marginally significant increase (p=0.07) in FSHR 680 Ser/Ser genotype frequency (0.25) was observed in the long-lived women compared to control women (0.08). The crude OR for the probability of surviving to age 90 years or older associated with the FSHR 680 Ser/Ser genotype, calculated only for women, was 3.75 (95% CI 1.00-314.03, p=0.039), suggesting that carrying the FSHR 680 Ser/Ser genotype favors the survival of women to 90 years and older. In contrast, no difference in the FSHR 680 genotype frequencies was observed between the long-lived and the control males. Table Estimates of the Effects of PPARG Pro la Genotypes on the Probability A of Surviving to Age over Years in Men Table and Pro la Genotype 1. FSHR 680 PPARG 12A Distribution in Long-Lived Subjects and Controls Males Females Long-lived Controls Long-lived Controls FSHR 680 No. (%) No. (%) No. (%) No. (%) genotypes Asn/Asn 8 (22) 8 (19) 22 (37) 13 (36) Asn/Ser 20 (54) 24 (59) 22 (37) 20 (56) Ser/Ser 9 (24) 9 (22) 15 (25) 3 (8) p=0.92 0.07 PPARG genotypes Pro/Pro 45 (92) 41 (79) 57 (88) 37 (93) Pro/Ala 3 (6) 11 (22) 7 (11) 3 (8) Ala/Ala 0 0 1 (2) 0 p=0.03,0.62 Variable OR, Odds ratio; CI, confidence interval. In the long-lived men compared to control men, no significant difference in PPARG Pro12Ala genotype frequencies was observed (0.22). The crude OR for the probability of surviving to age 90 years or older associated with the PPARG Pro/Ala genotype, calculated only for men, was 0.248 (95% CI 0.065-0.954), indicating that carrying the PPARG Pro/Ala genotype could limit survival to 90 years or older in men. Conversely, no difference in PPARG Pro12Ala genotype frequencies was observed between the long-lived and the control women. Logistic regression analysis was then applied to the female sample to correctly evaluate the effect of the FSHR 680 Ser/Ser genotype on longevity after adjusting for other covariates. In the analysis, the dependent variable was having survived to age over 90 years or not. Together with the FSHR 680 Ser/Ser genotype, the other explanatory variables were the estrogen receptor-a (ESR1) and aromatase (CYP19) genotypes that, in a previous study on the same sample, were observed to promote longevity in both men and women. Logistic regression analysis was then applied to the male sample to better evaluate the effect of PPARG genotypes on longevity after entering as further covariates the CYP19 and ESR1 genotypes, asage? This study examined the role of two genes, FSHR and PPARG, in longevity and their possible gender-specific effects. The FSHR gene was found to have a significant association with longevity in women, with the Ser/Ser genotype being more common in long-lived women compared to controls. This genotype has also been found to have a protective role against Alzheimer's disease in women. The PPARG Pro/Ala genotype was associated with lower longevity in men, independent of fertility level. However, the PPARG gene may have an age-dependent effect and may be involved in susceptibility to age-related diseases. Overall, there is a growing body of evidence supporting the need to consider gender-specific mechanisms in aging and longevity.Longevity? Italian Multicenter Study on Centenarians (IMUSCE). Aging;  Passarino G, Montesanto A, Dato S, Giordano S, Domma F, Mari V, Feraco E, De Benedictis G. Sex and age specificity of susceptibility genes modulating survival at old age. Hum Hered;  By comparison, genes associated with female longevity are not only fewer but tend to be more heterogeneous in function as well: some are involved in the basic pathways of aging, such as immune function and inflammation, others possibly involved in fertility or susceptibility to postmenopausal diseases (FSHR), and still others that preserve a healthy status during the reproductive years, thus favoring Corbo RM, Ulizzi L, Piombo L, Scacchi R. Study on a possible effect of four longevity candidate genes (ACE, PPAR-c, and APOE) on human fertility.;  Capri M, Salvioli S, Monti D, Caruso C, Candore G, Vasto Olivieri F, Marchegiani F, Sansoni P, Baggio G, Mari Passarino G, De Benedictis G, Franceschi C. Human longevity within an evolutionary perspective: the paradigm of a post-reproductive genetics. Exp;  De Rango F, Dato S, Bellizzi D, Rose G, Marzi E,L., Franceschi C,Skytthe A,Jeu ne B,Cournil A,Gampe J,Vaupel JW,Mari V,Feraco E,Passarino G,Velletto A, De Benedictis G. A novel sampling design to explore gene-longevity associations: the ECHA study. Eur Hum Genet.;  Rendina D,Gianfrancesco F,D e Filippo G,M erlotti Esposito T,Mingione A, Nuti R,Strazzullo P,Mossetti Gennari L. FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal Eur J Endocrinol;  Lussiana C, Guani B,Mari C,Restagno