Contents lists are available at the SciVerse ScienceDirect Experimental Gerontology journal homepage: www.elsevier.com/locate/expgero. Human longevity is a complex, heritable genetic trait. Based on substantial evidence from model organisms, it is clear that mitochondria play a pivotal role in aging and lifespan. However, the effects of mitochondrial genome variations on longevity and longevity-related phenotypes in Chuang people in China have yet to be established. By genotyping 15 variants for 10 haplogroups in 738 Chuang subjects, including 367 long-lived individuals and 371 controls, we found that haplogroup F was significantly associated with longevity in females of the Zhuang population of China (p=0.003, OR: 2.01, 95%CI: 1.26-3.19). Additionally, haplogroup F was related to higher HDL levels (p<0.05) in long-lived individuals. Further analysis suggests that the non-synonymous variant m.13928GNC in haplogroup F was also associated with longevity in female Zhuang Chinese, which might account for the beneficial effect of F. 

Longevity and successful aging are complex traits influenced by multiple genetic and environmental factors (Christensen et al., 2006; Glatt et al., 2007). A better understanding of mechanisms for successful aging and longevity has important implications for lowering the risk of age-related diseases and disability. Studies in model organisms have found hundreds of genetic variants that lead to life extension. Population studies have suggested that genetics contribute to variations in human lifespan by approximately 25% (Christensen et al., 2006). However, the mechanisms by which genetics contribute to human longevity and successful aging are still not clear.

A growing body of evidence indicates that mtDNA variants play a pivotal role in the aging process. For example, some mtDNA mutations or haplogroups (i.e., the combination of several common mtDNA variants) are associated with age-related degenerative diseases (Chinnery et al., 2001; Feder et al., 2009; Fuku et al., 2007; Tanaka, 2002; van der Walt et al., 2003). However, others are associated with increased longevity, such as 9055A in the French (Ivanova et al., 1998) and Irish, 5178A (Tanaka et al., 1998) in the Japanese, and 150T in the Irish, Finnish, and Japanese (Niemi et al., 2003, 2005; Zhang et al., 2003). MtDNA can be divided into haplogroups according to the ancient polymorphisms present in its coding region and D-loop. The European population is almost distributed among the nine haplogroups designated as H, I, J, K, T, U, V, W, and X. In contrast, haplogroups A, B, C, D, F, and G and certain subclusters of macrohaplogroups M and N are characteristic of Asian populations. Haplogroups A, B, C and D are specific to Amerindian populations and haplogroups L1, L2 and L3 to African populations.

MtDNA haplogroup J confers a higher chance to attain longevity than other mtDNA haplogroups in three independent populations in Northern Italy, Northern Ireland, and Finland (De Benedictis et al., 1999; Niemi et al., 2003; Ross et al., 2001). A significant enrichment of subhaplogroups D4a, D5 and D4b2b was shown in long-living Japanese individuals (Alexe et al., 2007; Bilal et al., 2008).

The study subjects were from Bama, China, and included 474 long-lived individuals and 264 controls. The long-lived group comprised 107 men and 367 women (mean [SD] age: 97.5 [6.03] and 94.3 [5.53] years old for men and women, respectively; range: 90-111 years old). The control group comprised 107 men and 264 women (mean [SD] age: 47.0 [5.11] and 46.6 [4.65] years old for men and women, respectively; range: 35-65 years old). All subjects from Bama were unrelated and belonged to the Zhuang population, which is one of the largest ethnic groups in mainland China with approximately 15,000,000 persons; it is second only to the Han population.

Additionally, circumstantial evidence suggests that mtDNA variations could influence aging and longevity either by bearingmutations that can modulate mitochondrial function or rely on complex relationships between mitochondrial and nuclear genomes (Santoro et al., 2006). Cybrid cell models have shown that mtDNA haplogroups H or J can differently modulate the expression of some nuclear genes related to the stress response, such as interleukin-1, tumor necrosis factor receptor 2, and interleukin-6, not only under basal conditions but also under oxidative stress conditions (Bellizzi et al., 2006; Santoro et al., 2006).

Standard demographic indicators of quality of age reporting in the Chuang population in China were 100.1±104.3 and 2.3±2.9, respectively, based on the 1982, 1990, and 2000 census data (Zeng, 2009). According to the United Nations' criteria, a Whipple's Index >105 and a Myer's Index >10 indicate good quality of age reporting. Thus, we are confident that the age information of the subjects who belong to Chuang ethnic group recruited in this study is reliable. In the control group of this study, we excluded individuals with one or two parents who survived to 90 years old or above, and in fact, they were not able to be randomly chosen. Twelve baseline and metabolic indexes such as age, gender, weight, height, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), serum total triglyceride (TG), serum total cholesterol (TC), HDL-cholesterol (HDL-c), and LDL-cholesterol (LDL-c) were measured in all selected longevity and control subjects.