The observed association could be due to LD either with a functional variant of the SIRT3 gene itself or of other genes occurring in this neighborhood. Negative findings obtained in LD analysis (Tables 1-4) show that the relationship between the G477T marker of SIRT3 and survivorship is not due to gene/longevity associations previously found in the same 11p15.5 region, thus reinforcing the hypothesis of D-linkage between the G477T variant and an unknown functional variant of SIRT3 itself. 

Whatever the functional variant may be, an association between a marker of SIRT3 and survivorship has been found. The possibility that the Sir2p human homologue has a role in aging is in line with the idea that modulators of the rate of aging are conserved over large evolutionary distances (Partridge and Gems, 2002). These findings indicate that Sir2p activity may be an evolutionary conserved check point of this complex interplay (Chang and Ming, 2002) and therefore agree with the idea that SIRT3 is a strong candidate in longevity taking into account findings in model organisms.Variability may modulate human aging. Additionally, the localization of the SIRT3 protein to mitochondria is in line with models that put mitochondria as central actors in the network connecting metabolic rate, gene expression modulation, and lifespan. HUMTHO.1-STR alleles are named according to the number of STR repeats; allele 10* contains the imperfect repeat (De Luca et al., 2001; Tan et al., 2002). Haplotypic frequencies are estimated by the maximum likelihood method (Arlequin 1.1 software). The hypothesis D=0 is not rejected (p=0.482 ^ 0.002).

4. Discussion
By applying a demographic-genetic approach (Yashin et al., 1999), a significant variation of survivorship was found in the elderly related to the genotypes defined by the G477T polymorphism of the SIRT3 gene. Although it is possible that such an association is due to chance, the statistical significance of the finding seems to indicate otherwise. The location of five genes potentially involved in human aging (HRAS1, SIRT3, IGF2, INS, TH) in a restricted chromosomal region, 11p15.5, is intriguing and suggests an evolutionarily conserved control of shared regulatory elements (Hurst et al., 2002). Some preliminary results obtained by gene expression studies indicate that this may be the case at least for some of the above 11p15.5 genes (Bellizzi et al., 2002). 

In conclusion, a demographic genetic approach has discovered a male-specific relationship between a marker of SIRT3 and survivorship. This finding shows that variability of a gene which affects lifespan in experimental organisms is associated with longevity in humans. Furthermore, SIRT3's chromosomal location close to other genes associated with longevity opens intriguing questions about the significance of this finding in the light of current evolutionary theories on aging and longevity (Partridge and Gems, 2002).

5. Supplementary material
The following supplementary material is available on the website of the Department of Cell Biology of the University of Calabria: http://biologia.unical.it/genetica. 
A graph reporting the survival curve of the general Italian population (year 2000) 
Genotypic distribution in the male population (x2=2.22 with 1 d.f.; p=0.155)
GG 152, 0.51 ^ 0.029, 157.1
GT 128, 0.43 ^ 0.029, 117.8
TT 17, 0.06 ^ 0.013, 22.1
Total: 297, 1, 297.0

Genotypic distribution in the female population (x2=3.28 with 1 d.f.; p=0.068)
GG 197, 0.45 ^ 0.024, 205.1
GT 202, 0.47 ^ 0.024, 185.8
TT 34, 0.08 ^ 0.013, 42.1
Total: 433, 1, 433.0

Alleles Counts Relative frequency ^ SE 
Allelic distribution in the male population 
G -432,0.73 ^0.018 
T-162,0.27^0.018 
Total-594,1 

Allelic distribution in the female population 
G-596,0.69^0.016 
T-270,0.31^0.016 

Survival Function 
Italian Population females~--males 
Age (Years) 
2.A map of the chromosome11p15.5 region, showing the in-scale position of the genes HRAS1, SIRT3, IGF2, INS and TH x2 and p-values refer to expected values at Hardy Weinberg Equilibrium (HWE). 

References:
Ardlie, K.G., Kruglyak, L., Seielstad, M., Patterns of linkage disequilibrium in the human genome. Nat. Rev. Genet., 2002.
Bellizzi, D., Rose, G., Maggiolini, M., Passarino, G., De Benedictis, G., The SIRT and the PSMD genes are linked head-to-head and share a bidirectional promoter. Proceedings of the Cold Spring Harbor Laboratory Molecular genetics of aging, October 2001, Cold Spring Harbor, NY, USA.
Bonafe`, M., Barbi, C., Olivieri, F., Yashin, A.I., Andreev, K.F., Vaupel, J.W., De Benedictis, G., Rose, G., Carrieri, G., Jazwinski, S.M., Franceschi, C., An allele of HRAS variable numberI'm sorry, there is no text enclosed in ``` ``` for me to proofread and improve. Please provide the text you want me to work on.