D4, D4b2b andD4a (Alexe et al., 2007) have been observed in Japanese centenarians. In addition, an increased incidence of D4a, and decreased incidences of M9, N9 and B4a haplogroups were observed in Chinese longevous subjects in Rugao (Cai et al., 2009). However, several of these associations were limited to specific populations and could not be replicated in other studies. For instance, unlike the findings of Tanaka et al. (2000) in a Japanese sample, an association between longevity and mtDNA 5178CNA polymorphism was not found in Chinese subjects (Yao et al., 2002b). Furthermore, compli- cated relationships between mtDNA haplogroups and longevity, Parkinson's disease, Alzheimer's disease or Type 2 diabetic have been demonstrated with several mtDNA haplogroups, including B5b and M7b2, found to be enriched in both longevous and disease groups (Takasaki, 2009). These seemingly discrepant findings may be attributed to a number of factors: sampling strategy limitations, such as inadequate matching of cases and controls, inadequate adjustment for multiple comparison testing, and cryptic population stratification (Shlush et al., 2008); interactions between mtDNA and the environment, for example, altitude may affect mtDNA haplogroup J2 enrichment in elderly people (Dominguez-Garrido et al., 2009); finally, mtDNA and variants elsewhere in the genome may interact. Moreover, the latter two factors usually related to specific populations and then create such paradoxes.

4. Discussion

The present results indicate that the C150T polymorphism is not robustly associated with longevity in Han Chinese populations we have investigated. Pearson Chi-Square analysis revealed that the two populations in this study had similar mtDNA genetic backgrounds and showed no differences in the overall haplogroup frequencies (data not shown). A similar situation occurred in another study on longevity in a Chinese population (Cai et al., 2009). However, we still cannot rule out that other mtDNA variants might be associated with human longevity potentially, despite the negative results found presently.

The mtDNA haplogroup structure in European populations is distinct from that in East Asian populations because of their different main haplogroups. In the European human mtDNA phylogeny tree, the C150T mutation defines haplogroup J2 and some sub-branches of haplogroup U and T (van Oven and Kayser, 2009), while it also acts as a motif site in 10 haplogroups in the East Asian tree. Additionally, we noticed that the C150T mutation frequencies in European populations reported by previous longevity related case/control studies were 17% vs. 3.4% in Italians (Zhang et al., 2003), 20.4% vs. 14.5% in Finns (Niemi et al., 2005) and 1.6% vs. 3.4% in Ashkenazi Jews (Iwata et al., 2007), for cases and controls, respectively. In contrast, the Chinese population in our study showed much higher frequencies (higher than 20%) of the C150T mutation in both case and control groups. As for other East Asian population, a research based on Japanese population found a significant higher frequency of C150T mutation in centenarians (19.79%) than in middle-aged controls (9.37%) (Niemi et al., 2005). Compared to the Han Chinese population, the C150T mutation frequency in Japanese population was near in case but obviously lower in control (Table 3). More importantly, their p-values were unadjusted for multiple comparisons and the sample size was small. Besides, the frequencies of the D5, M7b and N9a haplogroups in current study were roughly analogous to those observed in a longevous Chinese population in Rugao (Cai et al., 2009). Thus, if there was a real function of the C150T mutation that could affect human lifespan, it might be easier to detect in Chinese populations than in Europeans; furthermore, the possibility of introducing statistical bias would be smaller as well.

MtDNA is likely to play an important role in human ageing, although most investigations thus far remain within the scope of case/ control studies and the incidence difference was typically the only parameter that could be analyzed. However, there has been little focus on elucidating the mechanisms by which mtDNA variants could impact function at the cellular, tissue, or systems level, and thereby influence human lifespan. Functional studies on mtDNA variants are required that will help to further our understanding of the influence of mitochondrial/nuclear genetic background and environmental factors on human longevity.

Acknowledgements

We are greatly indebted to the persons who participated in this research. In addition, we thank Dr. Hui Li and Dr. Yuanying Gong for their help in sample collection, and Dr. Wendy Adams's help in preparing the paper. This work was supported by the National Basic Research Program of China (No. 2007CB507405), “Light in Western China” of the Chinese Academy of Sciences, the National Natural Science Foundation of China (No. 30621092), and the Bureau of Science and Technology of Yunnan Province.

References

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