Nowadays, no single or fixed trait of genes has enough evidence for being involved in the aging process.50 In contrast, there is some evidence that several genes may influence long- evity in humans.50,51 Furthermore, the genetic studies of human life span have several advantages and disadvantages. Human genetic studies have various study designs such as linkage anal- ysis (genetic mapping in humans), candidate-gene association studies, and longitudinal studies. The difficulty with linkage analysis is that it requires large studies. Concerning the candidate-gene association studies, they usually compare the genotypes of patients with exceptional longevity with younger individuals and also have similar limitations, the most serious being the lack of replication. In the longitudinal studies, the study cohort is followed for years and thus these studies are less prone to biases than candidate-gene association studies.

According to NFkB gene polymorphism, some studies have suggested that it is involved in aging. Helenius et al31 and Korhonen et al32 reported that NFkB DNA binding activity increases with age in rodent tissues. Also, Adler et al33 verified that NFkB DNA binding activity is induced with age in mouse skin, heart, kidney, liver, and spleen. Bernard et al34 induced senescence in primary human keratinocytes. The NFkB is play- ing a direct role in aging, in particular aging-induced gene expression and cellular senescence. Wang et al35 in their meta- analysis found that the Del/DelNFkB gene polymorphism might be associated with a decreased cancer risk, especially for Asian populations. This may have potential influence on human life span, since the risk of cancer increases with age. However, in our study, we did not find any difference in genotypes/allele

The current study is a candidate-gene association study that compared nonagenarians and centenarians with younger individuals with no possible prediction of their future longev- ity. Also, the number of participants is relatively small but

we should keep in mind that the nonagenarians and centenar- ians are usually not very enthusiastic to visit hospitals unless it is an urgent healthy problem.52 Finally, we did not have ACE and CETP levels measured in our cohorts. On the other hand, our study has some strength. We performed a second PCR to avoid a misclassification of heterozygotes as homozygotes. In addition, we studied a reasonably homogenous group of individuals according to geographical and ethnic origin (the majority of nonagenarians and centenarians were from Athens).

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Glas J, To¨ro¨k HP, Tonenchi L, et al. Role of the NFKB

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Conclusions

The present study reported that there are differences in the frequency of alleles in the oldest 2 decades (nonagenarians and centenarians) compared to middle-aged patients. Understand- ing aging at a molecular level could provide an option to slow this process and extend life span.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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