Hardy-Weinberg equilibrium was tested using a test. All statistical analyses were performed using PASW (v.18.0 for WINDOWS, Chicago). Genotype/allele frequencies were compared among the four study groups (centenarians, controls, endurance and power athletes) using a x2 test with a set at 0.05. We used logistic regression analysis to analyze the association between alleles and longevity after adjusting for sex.

The sample of elite endurance athletes included the best 50 professional male Spanish road cyclists (aged 26-63 years) in recent years, i.e., all Tour de France participants.

There were no failures in sample collection, DNA acquisition, or genotyping procedures, except for 5 centenarians for which the amount of DNA gathered from saliva was insufficient to allow ACTN3 R577X genotype assessment. Parallel genotyping results showed 100% concordance between the two laboratories.

Although the allelic/genotypic frequency of the ACTN3 R577X polymorphism did not significantly differ between centenarians and the control population, a major finding of our study was that overall, the allelic/genotypic distribution of the ACTN3 R577X polymorphism in centenarians was closest to that of those humans who arguably show the most extreme muscle endurance phenotypes, i.e., professional road cyclists able to excel in such demanding events as the Tour de France [10]. Notably, the frequency of the null XX genotype in our cohort of centenarians (24%) was the highest ever reported in non-athletic Caucasian populations and is only surpassed by the values of the professional road cyclists we studied (26%) and the elite endurance athletes cohort (made up of various types of Olympic-class endurance athletes, including road cyclists) of a previous report by Yang et al on Australian athletes (30%) [9].

Genotype and allele frequencies were compared among study groups (all P < 0.1). The ACTN3 R577X genotype distributions in our healthy controls were overall similar to those previously reported in healthy Spanish adults [10] and European Caucasians, i.e., 18% frequency of the XX genotype [7]. There were no differences in genotype or allele frequencies between centenarians and controls or endurance athletes (all P < 0.1). We repeated the analyses by comparing X carriers vs. non-X carriers or R carriers and non-R carriers and found no significant differences between groups (all P < 0.1). However, we observed significant differences in genotype and allele frequencies between centenarians and power athletes: the frequency of X carriers was higher in the centenarians compared with the power athletes group (Figure 1, P = 0.011), and the frequency of the X allele was also higher in centenarians than in power athletes (Figure 2, P = 0.019).

Although natural selection in the human genome accelerated during the past 40,000 years, probably less than 1% of our genes arose during the late Pleistocene and Holocene epochs (126,000-8,000 years before present), that is, after the Paleolithic era [4]. Genetically, therefore, we are still citizens of the Paleolithic era livingThe text appears to be in good shape with no major errors. However, there are a few minor errors that could be corrected for improved readability and clarity. Here is the processed text:

The ACTN3 gene has been associated with muscle function and athletic performance. The R577X polymorphism of this gene results in the absence of alpha-actinin-3 protein in homozygotes (XX genotype), which has been linked to an enhanced endurance phenotype in athletes. Studies have shown that the absence of alpha-actinin-3 leads to an increased contribution of slow-twitch (type I) muscle fibers and a shift towards oxidative metabolism. This phenotype is commonly observed in professional road cyclists who exhibit high aerobic capacity and muscle efficiency. The XX genotype is especially prevalent (26%) in this population.

Research has also shown that the metabolic effects of ACTN3 genotype may modify disease severity. The X allele has been found to benefit exercise capacity phenotypes in women with muscle disease. Our study found that the ACTN3 genotype profile of centenarians resembles that of world-class elite endurance athletes, suggesting a survival advantage brought about by alpha-actinin-3 deficiency and the endurance/oxidative muscle phenotype associated with it. However, more data on larger cohorts and other ethnicities are necessary.

Centenarians are a well-accepted group for identifying genetic factors associated with longevity assurance as they represent the survival tail of the population. Our study found similarities between the ACTN3 genotype profile of centenarians and world-class elite endurance athletes, while differing from that of elite power athletes. Identifying genetic variants associated with exceptional longevity and rate of physical function decline is important for potential medical relevance, especially since the oldest old is the most rapidly growing age group in western countries.

Our findings suggest that some genetic polymorphisms, such as ACTN3 R577X, which influence muscle function, may play a putative role in human survival. However, our results should be taken with caution due to the relatively low number of centenarians we studied. Future studies with larger samples of centenarian males and female athletic cohorts are necessary to corroborate our findings. Longevity is likely a complex, polygenic trait influenced by numerous gene-environment and gene-gene interactions.Sorry, there is no text enclosed in ``` ```. Please provide the text that needs to be proofread and improved.