Contents lists are available at the ScienceDirect Clinica Chimica Acta journal homepage: www.elsevier.com/locate/clinchim. Variants that are associated with aging in a healthy Han Chinese population. Wei-Guang Zhang a, Xiao-Juan Bai a, b, Xiang-Mei Chen b. a Departments of Gerontology and Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. b Department of Kidney, General Hospital of Chinese PLA, Beijing, China.

Background: Aging is influenced by diverse environmental and genetic risk factors. The SIRT1 (silent information regulator 1) gene has been shown to regulate lifespan and aging in previous studies. We determined whether variation in the SIRT1 gene is associated with aging in a healthy Chinese population.

Methods: The study population comprised 482 healthy, unrelated Chinese subjects, of which 246 were aging individuals from 60 to 91 years old, and 236 were younger individuals from 35 to 59 years old. All subjects were from Shenyang, China. Two single-nucleotide polymorphisms (SNPs) were analyzed: rs3758391 near the 5' end of the SIRT1 gene; and rs4746720 in the 3' untranslated region.

Results: Differences in allele and genotype frequency were seen between the groups; rs3758391/C was more common than rs3758391/T in the aging subjects (odds ratio=1.453, p=0.026), and rs3758391/CC was more common than rs3758391/CT and rs3758391/TT in the aging subjects (odds ratio=3.042, p=0.027). For the SNP rs4746720/C was more common than rs4746720/T in the aging subjects (odds ratio=1.347, p=0.022), and rs4746720/CC was more common than rs4746720/CT and rs4746720/TT in the aging subjects (odds ratio=1.461, p=0.049). The haplotype frequency distribution was also different, with haplotype CC more common in the older group (odds ratio=1.63, p=0.01).

Conclusion: These results suggest that SIRT1 gene polymorphisms may add a new factor to the multifactorial genetic contributions to aging.

Introduction: Aging is a progressive function decline process at the cellular and organism levels. The interaction of genetic and environmental factors contributes to the aging process. Genetic factors and lifespan correlate, implying a relatively strong genetic contribution to the human aging process [1,2]. Mammals possess seven sirtuins, encoded by SIRT1-SIRT7 [3,4]. The SIRT2 gene is the first gene discovered in the sirtuin family and was associated with extended life span in several organisms. SIRT1 is a mammalian NAD+-dependent deacetylase homolog of yeast SIRT2. The SIRT1 gene has been shown to regulate lifespan and aging in model organisms that include yeast, C. elegans, and rodents [5].

Research has been conducted on healthy aging populations, although SIRT1 is an important candidate gene for retarding aging and forestalling the onset of age-associated diseases [10,11]. Recently, the Leiden 85 plus extremely aging Study found that the rs3758391 T-allele of the SIRT1 gene was associated with high cognitive function in Dutch people [12]. But the Leiden 85-plus Study, a study conducted on German subjects and a study in a Belgian Caucasian population did not find that the SIRT1 sequence variation influenced exceptional extremely aging in the German, Dutch, and Belgian populations [12-14]. An association study of SIRT1 gene variation and visceral obesity in Belgian Caucasians found that the rs7069102 C-allele of SIRT1 is associated with reduced risk of obesity [13]. Since obesity may accelerate the aging process [15], SIRT1 gene variability may contribute to changes in SIRT1 and correlate with the aging process.

SIRT1 antagonizes cellular senescence by activating ERK/S6K1 signaling in human diploid fibroblasts [6]. The SIRT1 activator resveratrol extends lifespan and improves glucose homeostasis in mice by stimulating SIRT1-mediated deacetylation of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) [7]. Increased SIRT1 expression promotes survival and suppresses age-dependent transcriptional changes in a mouse model of genomic instability. A moderate increase in SIRT1 confers resistance to aging-related oxidative stress and apoptosis and appears to be beneficial for aging [8,9].

Since the results obtained in other populations wereBased on previous study reports, the SNPs associated with aging were analyzed by neighborhood to provide residents with a self-evaluation list of basic health. A random sample survey was conducted according to sex and age, and those who met the inclusion criteria underwent a past disease investigation, physical examination, investigation of brain functions, specimens from blood and urine samples, testing blood, urine and blood biochemistry, electrocardiogram, chest X-ray and cardiovascular ultrasound. The selected subjects also completed a living conditions and food frequency questionnaire. If the selected object is less than the required tasks, then another 130% random sample survey is conducted according to sex and age. Fig. 1 shows the healthy subjects selection process. The SNPs rs3758391 and rs4746720 in different age groups were analyzed by capillary electrophoresis using an ABI3730 (Applied Biosystems, Foster City, CA) DNA analysis system and Gene Mapper 4.0 software (Applied Biosystems). The genotype and allele frequencies of these SNPs were compared between young subjects (n=236) and aging subjects (n=246). Statistical analyses were performed by SPSS software package (SPSS ver. 13.0, Chicago, IL), and the Pearson's chi-square test was used to compare genotype, alleles and haplotype frequencies in both groups. A p-value < 0.05 was considered significant.