Individuals who live to 85 and beyond without developing major age-related diseases may achieve this, in part, by lacking disease susceptibility factors, or by possessing resistance factors that enhance their ability to avoid disease and prolong lifespan. Healthy aging is a complex phenotype likely to be affected by both genetic and environmental factors. We sequenced 24 candidate healthy aging genes in DNA samples from 47 healthy individuals aged eighty-five years or older (the ‘oldest-old’), to characterize genetic variation that is present in this exceptional group. These healthy seniors were never diagnosed with cancer, cardiovascular disease, pulmonary disease, diabetes, or Alzheimer disease. We re-sequenced all exons, intron-exon boundaries and selected conserved non-coding sequences of candidate genes involved in aging-related processes, including dietary restriction (PPARG, PPARGC1A, SIRT1, SIRT3, UCP2, UCP3), metabolism (IGF1R, APOB, SCD), autophagy (BECN1, FRAP1), stem cell activation (NOTCH1, DLL1), tumor suppression (TP53, CDKN2A, ING1), DNA methylation (TRDMT1, DNMT3A, DNMT3B) Progeria syndromes (LMNA, ZMPSTE24, KL) and stress response (CRYAB, HSPB2). We detected 935 variants, including 848 single nucleotide polymorphisms (SNPs) and 87 insertion or deletions; 41% (385) were not recorded in dbSNP. This study is the first to present a comprehensive analysis of genetic variation in aging-related candidate genes in healthy oldest-old. These variants and especially our novel polymorphisms are valuable resources to test for genetic association in models of disease susceptibility or resistance. In addition, we propose an innovative tagSNP selection strategy that combines variants identified through gene re-sequencing- and HapMap-derived SNPs.

Several genes have been identified as important in athletic performance. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been related to improvements in performance and exercise duration. However, there are large divergences among studies on the influence of ACE I/D polymorphism on physical performance. Other studies have demonstrated that strenuous exercise generally overloads the endogenous antioxidant system's capacity, leading to oxidative damage to muscles and other tissues in athletes. Few studies have reported significant associations between glutathione S-transferase (GST) deletion polymorphisms and resistance performance in athletes. We examined the effects of ACE I/D and GST deletion polymorphisms in young soccer players in central Brazil. We included 65 soccer players from under-20 (18 to 20 years old) soccer ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 18 (2): gmr18192 W.C.F. Menezes et al. 2 teams and 60 non-athletes in a case-control study. All subjects had their physical performance investigated through the Running-based Anaerobic Sprint Test (RAST). Genotyping was performed using real-time PCR. We found that the I/D genotype was significantly more frequent in athletes compared with the non-athletes. Individuals with the ID and DD genotypes had an approximately 3.13-fold and 4.37-fold increase in strength and power-orientated performance, respectively. The DD genotype in athletes presented RAST-test results considered as excellent to good when compared with non-athletes. When we examined a possible association of the GST deletion polymorphisms and RAST test, we found no influence on athletic performance. We did find association between ACE I/D polymorphism and athletic performance. However, there was no association between GST polymorphisms and risk of oxidative damage in the muscles. Our findings may help to select young players with the most favorable genetic potential to succeed as soccer athletes.