Carmen Fiuza-Luces

Genomics of elite sporting performance: what little we know and necessary advances.

Numerous reports of genetic associations with performance-related phenotypes have been published over the past three decades but there has been limited progress in discovering and characterising the genetic contribution to elite/world-class performance, mainly owing to few coordinated research efforts involving major funding initiatives/consortia and the use primarily of the candidate gene analysis approach. It is timely that exercise genomics research has moved into a new era utilising well-phenotyped, large cohorts and genome-wide technologies—approaches that have begun to elucidate the genetic basis of other complex traits/diseases. This review summarises the most recent and significant findings from sports genetics and explores future trends and possibilities.

Exercise attenuates the major hallmarks of aging.

Regular exercise has multi-system anti-aging effects. Here we summarize how exercise impacts the major hallmarks of aging. We propose that, besides searching for novel pharmaceutical targets of the aging process, more research efforts should be devoted to gaining insights into the molecular mediators of the benefits of exercise and to implement effective exercise interventions for elderly people.

Exercise Training and Cytokines in Breast Cancer Survivors

The purpose of this randomized controlled trial was to determine the effects of an 8-week (aerobic+strength) exercise training program (3 sessions/week) on the circulating cytokine levels of breast cancer survivors. We randomly allocated 16 female survivors of breast cancer (mean±SD age: 50±5 years) to an intervention or usual care (control) group (N=8 in each group). The intervention group followed an 8-week exercise program consisting of 3 sessions/week (session duration: 90 min). We measured the levels of the following cytokines before and after the intervention: beta-NGF, CTACK, eotaxin, FGF basic, G-CSF, gmCSFα, HGF, ICAM1, IFNα2, IFNγ, IL1α, IL1ß, IL1ra, IL2, IL2ra, IL3, IL4, IL6, IL7, IL8, IL9, IL10, IL12, IL13, IL15, IL16, IL17, IL18, IP10, LIF, MCS-F, MIP1α, MIP1β, MIF, MCP1, MCP3, MIG, PDGF bb, SCF, SCGFβ, SDF1α, TRAIL, TNFα, TNFβ, VCAM1, and VEGF. We only observed a significant interaction (group*time) effect for CTACK ( P=0.016), with mean values remaining stable in the intervention group but increasing over time in controls. The intervention program did not induce a significant decrease in the main breast cancer-related cytokines such as IL6 and IL8. A combined (aerobic+strength) 8-week exercise training intervention did not induce major changes in the basal cytokine levels of breast cancer survivors.

Aerobic fitness is associated with lower risk of hospitalization in children with cystic fibrosis

Children with cystic fibrosis (CF) often have to be hospitalized because of acute exacerbation of their respiratory symptoms. Given the fact that improved peak oxygen uptake (VO2peak) is positively associated with lung function and overall health in children with CF, this study examined the association between VO2peak and the need for hospitalization in a cohort of pediatric CF patients.

The K153R Polymorphism in the Myostatin Gene and Muscle Power Phenotypes in Young, Non-Athletic Men

The Lys(K)153Arg(R) polymorphism in exon 2 (rs1805086, 2379 A>G replacement) of the myostatin (MSTN) gene is a candidate to influence skeletal muscle phenotypes. We examined the association between the MSTN K153R polymorphism and ‘explosive’ leg power, assessed during sprint (30 m) and stationary jumping tests [squat (SJ) and counter-movement jumps (CMJ)] in non-athletic young adults (University students) [n = 281 (214 men); age: 21–32 years]. We also genotyped the MSTN exonic variants E164K (rs35781413), I225T, and P198A, yet no subject carried any of these variant MSTN alleles. As for the K153R polymorphism, we found only one woman with the KR genotype; thus, we presented the results only for men. The results of a one-way ANCOVA (with age, weight and height entered as covariates) showed that men with the KR genotype (n = 15) had a worse performance in vertical jumps compared with those with the KK genotype [SJ: vertical displacement of center of gravity (CG) of 35.17±1.42 vs. 39.06±0.39 cm, respectively, P = 0.009; CMJ: vertical displacement of CG of 36.44±1.50 vs. 40.63±0.41 cm, respectively, P = 0.008]. The results persisted after adjusting for multiple comparisons according to Bonferroni. Performance in 30 m sprint tests did however not differ by K153R genotypes. In summary, the MSTN K153R polymorphism is associated with the ability to produce ‘peak’ power during muscle contractions, as assessed with vertical jump tests, in young non-athletic men. Although more research is still needed, this genetic variation is among the numerous candidates to explain, alone or in combination with other polymorphisms, individual variations in muscle phenotypes.

Physical Inactivity and Low Fitness Deserve More Attention to Alter Cancer Risk and Prognosis

Sedentary lifestyle is associated with elevated cancer risk whereas regular physical activity (PA) and high cardiorespiratory fitness (CRF) have the opposite effect, with several biologic mechanisms mediating such associations. There is a need for lifestyle interventions aimed at increasing the PA levels and CRF of the general population and particularly cancer survivors. Furthermore, provocative data suggest a dose-dependent benefit of increasing levels of PA and/or CRF against cancer risk or mortality. Thus, current PA guidelines (≥150 min/wk of moderate-to-vigorous PA) may not be sufficiently rigorous for preventing cancer nor for extending cancer survivorship. Research targeting this issue is urgently needed. Promoting regular PA along with monitoring indicators of CRF and adiposity may provide powerful strategies to prevent cancer in populations, help patients with cancer more effectively deal with their disease and enhance secondary prevention programs in those who are affected by cancer. Cancer Prev Res; 8(2); 105–10. ©2014 AACR.

Are 'endurance' alleles 'survival' alleles? Insights from the ACTN3 R577X polymorphism.

Exercise phenotypes have played a key role for ensuring survival over human evolution. We speculated that some genetic variants that influence exercise phenotypes could be associated with exceptional survival (i.e. reaching ≥100years of age). Owing to its effects on muscle structure/function, a potential candidate is the Arg(R)577Ter(X) polymorphism (rs1815739) in ACTN3, the structural gene encoding the skeletal muscle protein α-actinin-3. We compared the ACTN3 R577X genotype/allele frequencies between the following groups of ethnically-matched (Spanish) individuals: centenarians (cases, n = 64; 57 female; age range: 100–108 years), young healthy controls (n = 283, 67 females, 216 males; 21±2 years), and humans who are at the two end-points of exercise capacity phenotypes, i.e. muscle endurance (50 male professional road cyclists) and muscle power (63 male jumpers/sprinters). Although there were no differences in genotype/allele frequencies between centenarians (RR:28.8%; RX:47.5%; XX:23.7%), and controls (RR:31.8%; RX:49.8%; XX:18.4%) or endurance athletes (RR:28.0%; RX:46%; XX:26.0%), we observed a significantly higher frequency of the X allele (P = 0.019) and XX genotype (P = 0.011) in centenarians compared with power athletes (RR:47.6%; RX:36.5%;XX:15.9%). Notably, the frequency of the null XX (α-actinin-3 deficient) genotype in centenarians was the highest ever reported in non-athletic Caucasian populations. In conclusion, despite there were no significant differences with the younger, control population, overall the ACTN3 genotype of centenarians resembles that of world-class elite endurance athletes and differs from that of elite power athletes. Our preliminary data would suggest a certain ‘survival’ advantage brought about by α-actinin-3 deficiency and the ‘endurance’/oxidative muscle phenotype that is commonly associated with this condition.

Are mitochondrial haplogroups associated with elite athletic status? A study on a Spanish cohort

There is increasing evidence regarding the association between mitochondrial DNA (mtDNA) and aerobic capacity; however, whether mtDNA haplogroups are associated with the status of being an elite endurance athlete is more controversial. We compared the frequency distribution of mtDNA haplogroups among the following groups of Spanish (Caucasian) men: 102 elite endurance athletes (professional road cyclists, endurance runners), 51 elite power athletes (jumpers, throwers and sprinters), and 478 non-athletic controls. We observed a significant difference between endurance athletes and controls (Fisher exact test=17.89, P=0.015; Bonferronis significant threshold=0.017), yet not between power athletes and controls (Fisher exact test=47.99, P=0.381) or between endurance and power athletes (Fisher exact test=5.53, P=0.597). We observed that the V haplogroup was overrepresented in endurance athletes (15.7%) compared with controls (7.5%) (odds ratio: 2.284; 95% confidence interval: 1.237, 4.322). In conclusion, our findings overall support the idea that mtDNA variations could be among the numerous contributors to the status of being an elite endurance athlete, whereas no association was found with elite power athletic status.

Is the −174 C/G polymorphism of the IL6 gene associated with elite power performance? A replication study with two different Caucasian cohorts

A functional −174 C/G polymorphism in the interleukin‐6 gene (IL6) is a candidate to explain individual variations in exercise‐related phenotypes. To replicate recent findings showing an association between the G allele and GG genotype of elite power sports performance in European (Spanish) Caucasian males, we compared allelic and genotypic frequencies of the IL6−174 C/G polymorphism among elite endurance athletes (n= 74) and power athletes (n= 81) and non‐athletic control subjects (n= 205) of both sexes from Israel. All subjects were Israeli Caucasians (with an equivalent ratio of non‐Ashkenazi and Ashkenazi descent in each group; 2:1). We found no differences in the genotype or allele frequencies among groups (all P > 0.3). We further compared the genotype and allele frequencies between national‐ (n= 109) and international‐level Israeli athletes (n= 46) in the endurance and power group, and found no significant genotype or allele differences after adjusting for multiple comparisons. We repeated all the analyses after pooling the Israeli and Spanish control subjects, endurance and power elite athletes, and found no genotypic and allelic differences among groups. The results did not change when the analyses were repeated including only the best Israeli athletes (i.e. the international‐level group) together with the group of elite Spanish athletes (P > 0.2). In conclusion, the results of the present study did not show an association between the G allele of the IL6−174 G/C polymorphism and power sports performance in the Israeli (Caucasian) population. Our findings support the need to replicate association results between genetic polymorphisms and athletic status in populations of different ethnic backgrounds with the largest possible population samples.

Physical function and quality of life in patients with chronic GvHD: a summary of preclinical and clinical studies and a call for exercise intervention trials in patients.

Allogeneic hematopoietic stem cell transplant, to reconstitute the hematopoietic and immune status of patients undergoing myeloablative therapy for hematologic disorders, has been of great benefit in minimizing or eradicating disease and extending survival. Patients who undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) are subject to many comorbidities among which the most significant, affecting quality of life (QoL) and survival, are acute GvHD (aGvHD) and chronic GvHD (cGvHD), resulting from donor lymphocytes reacting to and damaging host tissues. Physical activity and exercise have clearly been shown, in both children and adults, to enhance fitness, improve symptomatology and QoL, reduce disease progression and extend survival for many diseases including malignancies. In some cases, vigorous exercise has been shown to be equal to or more effective than pharmacologic therapy. This review addresses how cGvHD affects patients’ physical function and physical domain of QoL, and the potential benefits of exercise interventions along with recommendations for relevant research and evaluation targeted at incorporating this strategy as soon as possible after allo-HSCT and ideally, as soon as possible upon diagnosis of the condition leading to allo-HSCT.