The HWE test and linkage disequilibrium test were performed by Genepop 3.4 software [21] and Haploview software [18], respectively. The haplotype estimation was conducted by Phase 2.1 software [22,23]. Differences in allele and genotype frequency were observed between young and aging subjects for rs3758391/C (more common in aging subjects) and rs4746720/C (more common in aging subjects). Genotype distributions and allele frequencies showed no differences between genders. Statistical analysis on the SNP haplotypes showed that the CC haplotype was significantly increased in the aging group compared to younger individuals.

SIRT1 has been linked to increases in maximum lifespan mediated by calorie restriction. SIRT1 activates a critical component of calorie restriction in mammals, and calorie restriction activates SIRT1. SIRT1 interacts with the insulin/IGF-1 signaling pathway, promotes fat mobilization, improves insulin sensitivity, reduces the incidence of age-related disease, slows the pace of aging, and increases maximum lifespan. The interaction of SIRT1 with the NF-kappaB, FoxO and p53 signaling systems might resist stress, modulate aging-associated disease, delay the aging process and extend lifespan.

Previous studies have explored the relationship between SIRT1 gene polymorphisms and exceptional human longevity, cognitive functioning and Alzheimer's disease risk. However, little is known about the polymorphism of SIRT1 gene with healthy aging at present.

This work was supported by the National Basic Research Program of China (No.2007CB507405).

Table 1 shows the primers for rs3758391 and rs4746720 in SIRT1 gene. Table 2 shows the genotype and allele frequencies of these SNPs in different age groups. Table 3 shows the genotype and allele frequencies of these SNPs in different gender groups. Table 4 shows the haplotypes for rs3758391 and rs4746720 in SIRT1 gene.

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