Ito et al. reported that mice with ATM deficiency showed accelerated aging. However, a recent study done by Jaejoon Won et al. demonstrated that moderately reduced activity of the ATM gene could reverse senescence in BJ fibroblasts through inhibiting P53 signaling pathway. So the ATM gene has a double-edged role. Firstly, as a regulator of oxidative stress, it protects us from reactive oxygen species (ROS)-induced DNA damage. The other role is being a sensor of DNA damage, triggering cellular senescence, apoptosis, or transient cell-cycle arrest. Based on the findings above, we suggest that neither low expression nor high expression of the ATM gene is good for lifespan. Therefore, moderate levels of ATM expression may be the best way to prolong lifespan. Inconsistent with this opinion, our results show that the CT genotype, which shows moderate levels of ATM expression, is overrepresented in the long-lived group and noticeably, individuals with CT heterozygote have the potency to live long (Supplement Tables 1 and 2).

In conclusion, lifespan is the outcome of complicated processes involved in many genes and non-genetic factors (Christensen et al., 2006). In our study, all participants are from the same region (countryside), they have similar lifestyles, and confusing factors (non-genetic factors) are almost not presented. Genes are predominant factors for longevity; therefore, our results are reliable, and other polymorphisms associated with longevity may exist.