4. Discussion

By applying a demographic-genetic approach (Yashin et al., 1999) a significant variation of the survivorship, related to the genotypes defined by the G477T polymorph- ism of the SIRT3 gene, was found in the elderly. Although the possibility that such association is due to chance cannot be ruled out, the statistical significance of the finding seems

Table S1 SIRT3 (G477T) polymorphism Genotype Absolute Relative HWE expected frequency frequency ^ SE values —Contig NT_035113IGF2INS   

as well as its NAD þ dependent activity in these organelles, is in line with models putting the mitochondria as central actors in the network which connects metabolic rate, gene expression modulation, and lifespan (Salvioli et al., 2001; Rose et al., 2002).

The location in a restrict chromosomal region, 11p15.5, of five genes potentially involved in human ageing (HRAS1, SIRT3, IGF2, INS, TH) is very intriguing and suggests an evolutionary conserved control of shared regulatory elements (Hurst et al., 2002). Some preliminary results we 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, by a demographic genetic approach a male-specific relationship between a marker of SIRT3 and survivorship has been discovered. This finding shows that the variability of a gene which affects lifespan in experimental organisms is associated with longevity in humans. Furthermore, the SIRT3 chromosomal location close to other genes associated with longevity opens intriguing questions about the significance of this finding in the light of the current evolutionary theories on ageing and longevity (Partridge and Gems, 2002).

5. Supplementary material

The following supplementary material is available on the web site 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 ¼ 2.22 with 1 d.f.; p ¼ 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 ¼ 3.28 with 1 d.f.; p ¼ 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 frequenvy ^ 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 Function0.80.60.4  0.2Italian Population   — females~-- males       2040 60Age (Years) 

2. A map of the chromosome 11p15.5 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).

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