Mitochondrial DNA polymorphisms are associated with the longevity in the Guangxi Bama population of China

Xiurong Yang • Xinping Wang • Huilu Yao • Jixian Deng • Qinyang Jiang • Yafen Guo • Ganqiu Lan • D. Joshua Liao • Hesheng Jiang

Received: 22 November 2011/Accepted: 9 June 2012/Published online: 24 June 2012   Springer Science+Business Media B.V. 2012

total cholesterol, triglyceride and low density lipoprotein than did mt146C in the older age group (P \ 0.05). No significant differences were observed between the mt146C and the mt146T individuals in the middle and the younger groups (P [ 0.05). The mt5178C/A polymorphisms did not show any significant differences among the three age- groups (P [ 0.05), but different nationalities in the Bama County did show a significant difference in the mt5178C/A polymorphisms (P \ 0.05). These results suggest that the mt146T/C polymorphisms in Guangxi Bama individuals may partly account for the Bama longevity whereas the mt5178C/A polymorphisms are strongly associated with the nationalities in the Guangxi Bama population.

Abstract Human longevity is an interesting and com- plicated subject, with many associated variations, geo- graphic and genetic, including some known mitochondrial variations. The population of the Bama County of Guangxi Province of China is well known for its longevity and serves as a good model for studying a potential molecular mechanism. In this study, a full sequence analysis of mitochondrial DNA (mtDNA) has been done in ten Bama centenarians using direct sequencing. Polymorphisms of the displacement loop (D-loop) region of mtDNA and several serum parameters were analyzed for a total of 313 Bama individuals with ages between 10 and 110 years. The results showed that there were seven mitochondrial varia- tions, A73G, A263G, A2076G, A8860G, G11719A, C14766T, and A15326G, and four haplogroups, M*, F1, D* and D in 10 Bama centenarians. In the D-loop region 4 of mtDNA, the mt146T occurred at a significantly lower frequency in those is the older age group (90–110 years) than in the middle (80–89 years) and in the younger (10–79 years) groups (P \ 0.05). The mt146T also had lower systolic blood pressure and serum markers such as

Introduction

Mitochondria are the cellular organelles responsible for ATP synthesis, heat production, radical oxygen species (ROS) generation, fatty acid and steroid metabolism, cel- lular apoptosis, etc. Because of their critical role in energy production, mitochondria have been in the center of the studies on the mechanism for longevity [1]. Mitochondria have their own genetic material, mitochondrial DNA, a circular double-stranded molecule of 16,569 bp encoding two tRNAs, two rRNAs and 13 proteins [2]. Since mito- chondrial DNA (mtDNA) is maternally inherited and since the female has a longer lifetime than the male in various species [3–7], mtDNA has been suggested to have an important role in the process of aging and longevity.

H. Yao   J. Deng   H. Jiang China-ASEAN (Guangxi) Biotechnology Cooperative Center, Guangxi Academy of Sciences, Nanning 530003, People’s Republic of China

There is geographical variation in the numerous mtDNA inherited variants, some of which have been reported to

Materials and methods

ent populations are expected to have different gene-lon- gevity associations. There is evidence for mitochondrial bioenergetics contributing to longevity [11–14], and the mitochondrial theory of aging suggests that a progressive accumulation of somatic mutations leads to a decline in mitochondrial function [15, 16]. Previous studies suggest that a variety of deletions and mutations accumulates with age in mtDNA [12, 17]. An association has been reported between certain mtDNA haplogroups and longevity [18]. For instance, the frequency of haplogroup J is significantly higher among male centenarians in northern Italy [19] whereas the haplogroup U is more frequent in centenarians than in younger people in the European [9, 20]. The 3010A, 5178A and 8414T of mtDNA occur at higher frequencies in Japanese centenarians comparing with other genotypes at these sites [21], while the mt9055A is reported to be more frequent in centenarians than in the younger popu- lation in French [22] and Irish [23].

Population and sample collection

Blood samples were collected from a total of 313 indi- viduals in the longevity and non-longevity areas in Guan- gxi Bama Yao Autonomous County, Guangxi Province of China. Of the 313 individuals, 113 were in the 90–110 years of age, 75 between 80 and 89 years of age, and the remaining 125 were between 10 and 79 years of age. Information on demographics, marriage, reproduction, work and living habits psychological and physical func- tioning status, and dietary habits was also collected by interviewing each individual. Age records were obtained from birth registers and generation rankings. The blood samples and personal data were collected in compliance with the institutional guidelines and under a protocol approved by the Institutional Review Board of Guangxi University. Written informed consent was obtained from all study participants or from family representatives if the participants could not provide consent due to reasons such as illiteracy.