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journal homepage: www.elsevier.com/locate/expgero

of mtDNA haplogroup F with healthy longevity in the female Chuang

Feng a,b, Jianyi Zhang a, Ming Liu a, Gang Wan a, Keyan Qi a, Chenguang Zheng c, Zeping Lv d, Caiyou Hu ⁎ Zeng e,f, Simon G. Gregory g, Ze Yang a,

a Genetics Department, National Institutes of Geriatrics, Beijing Hospital, Ministry of Health P.R. China, Beijing 100730, b Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China c Guangxi Chuang Autonomous Women and Children Health Hospital, Nanning 530003, China d Guangxi Chuang Autonomous Jiangbin Hospital, Nanning 530012, China e Duke Center for Study of Aging and Human Development, Medical School of Duke University, Durham, NC 27710, USA f China Center for Economic Research, National School of Development, Peking University, Beijing 100871, China g Duke Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA

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 that mitochondrial genome variations have upon 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 longev- ity in females of Zhuang population of China (p=0.003, OR: 2.01, 95%CI: 1.263–3.197). Additionally, hap- logroup F was related to higher HDL levels (pb0.05) 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.

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1. Introduction

inheritance (Abbott et al., 1978; Brand et al., 1992; Korpelainen, 1999; Sont and Vandenbroucke, 1993) and because mitochondria play pivotal roles in energy production and metabolism, genetic variants associated with mtDNA are likely to be key genetic components that contribute to longevity and successful aging.

Longevity and successful aging is a complex trait that is by multiple genetic and environmental factors (Christensen et al., 2006; Glatt et al., 2007). A better understanding of mechanisms of successful aging and longevity has important implications for lowering the risk for age-related disease and disability. Studies in model organisms have found hundreds of genetic variants that lead to life extension. Population studies have suggested that the genetic contribution to variations in humanlifespanisapproximately25%(Christensenetal.,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 vari- ants) are associated with age-related degenerative diseases (Chinnery et al., 2001; Feder et al., 2009; Fuku et al., 2007; Tanaka, 2002; van der Waltetal.,2003).However,othersareassociatedwithincreasedlongev- ity, 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; Zhanget al., 2003). MtDNA canbe di- vided into haplogroups according to the ancient polymorphims present in its coding region and D-loop. The European population is almost dis- tributed among the nine haplogroups designated as H, I, J, K, T, U, V, W and X, whereas 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 and haplogroups L1, L2 and L3 to African populations. mtDNA haplogroup J confers a higher chance to attain longevity than other mtDNA haplogroups in

Human mitochondrial DNA (mtDNA) is a 16,569 bp double-stranded circular genome which is the only repository of genetic information out- side the nucleus. The mtDNA encodes for 22 tRNAs, 2 rRNAs and 13 pro- teins that are essential components for the assembly and function of the respiratory chain. Because longevity is characteristic of maternal

⁎ Corresponding author at: Genetics Department, National Institutes of Geriatrics, Beijing Hospital, Ministry of Health P.R. China, #1 Dahua Rd, Dongdan, Beijing 100730, China. Tel.: +86 10 5811 5043; fax: +86 10 6523 7929. E-mail address: fj79330@163.com (Z. Yang).

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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).

old for women and men, respectively; range: 90–111 years old). The control group comprised 264 women and 107 men (mean [SD] age: 46.6 [4.65] and 47.0 [5.11] years old for women and men, respectively; range: 35–65 years old). All subjects from Bama were unrelated and belonged to the Chuang 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.