Attenuation of cardiovascular adaptations to exercise in frail octogenarians.

To determine the mechanisms underlying increased aerobic power in response to exercise training in octogenarians, we studied mildly frail elderly men and women randomly assigned to an exercise group (n = 22) who participated in a training program of 6 mo of physical therapy, strength training, and walking followed by 3 mo of more intense endurance exercise at 78% of peak heart rate or a control sedentary group (n = 24). Peak O2 consumption (V(O2 peak)) increased 14% in the exercise group (P < 0.0001) but decreased slightly in controls. Training induced 14% increase (P = 0.027) in peak exercise cardiac output (Q), determined via acetylene re-breathing, and no change in arteriovenous O2 content difference. The increase in Q was mediated by increases in heart rate (P = 0.009) and probably stroke volume (P = 0.096). Left ventricular stroke work also increased significantly. In the men, the increase in V(O2 peak) was exclusively due to a large increase in peak Q (22%). In the women, the gain in V(O2 peak) was due to small increases in Q and O2 extraction from skeletal muscles. Pulse pressure normalized for stroke volume and arterial elastance during peak effort did not change with training. Controls showed no changes. The results suggest that, although frail octogenarians have a diminished capacity for improvement in aerobic power in response to exercise training, this adaptation is mediated mostly by an increase in Q during peak effort. Furthermore, Q likely plays a greater role in the adaptive increase in V(O2 peak) in old men than old women.     

RNAi-mediated depletion of the 15 KH domain protein, vigilin, induces death of dividing and non-dividing human cells but does not initially inhibit protein synthesis

Vigilin/Scp160p/DDP1 is a ubiquitous and highly conserved protein containing 15 related, but non-identical, K-homology (KH) nucleic acid binding domains. While its precise function remains unknown, proposed roles for vigilin include chromosome partitioning at mitosis, facilitating translation and tRNA transport, and control of mRNA metabolism, including estrogen-mediated stabilization of vitellogenin mRNA. To probe sites of vigilin action in vertebrate cells, we performed nucleic acid binding and RNA interference studies. Consistent with a potential role in chromosome partitioning, human vigilin exhibits a higher affinity for Drosophila dodecasatellite single-stranded DNA than for vitellogenin mRNA 3′-UTR. Direct observation and flow cytometry in non-mitotic, serum-starved, HeLa cells showed that RNAi-mediated vigilin knockdown is rapidly lethal, indicating an essential function for vigilin distinct from its proposed role in chromosome partitioning. Pulse labeling experiments revealed that rates of protein synthesis and degradation are unaffected by the several fold reduction in vigilin levels early in siRNA knockdown indicating that vigilin is not a global regulator of translation. These data show that vigilin is an essential protein in human cells, support the view that vigilin’s most essential functions are neither chromosome partitioning nor control of translation, and are consistent with vigilin playing a critical role in cytoplasmic mRNA metabolism.     

A role for moesin in polarity

Three groups have recently characterized defects arising in development owing to mutations in the gene encoding Dmoesin, which is the sole ezrin-radixin-moesin (ERM) protein in Drosophila. Previously, studies in cultured mammalian cells suggested that ERM proteins are important for actin-membrane associations. However, mutations in moesin and radixin in mice do not cause severe defects, indicating functional overlap among vertebrate ERM paralogs. In Drosophila, however, mutations in Dmoesin result in lethality. Actin organization in imaginal disc epithelia is abnormal and apical-basal polarity is lost. When moesin function is reduced in the female germ-line, defects in cortical actin organization are also observed. Localization of informational molecules at the oocyte posterior is strongly affected, thus indicating a role for moesin in anchoring these determinants.     

What makes an endurance athlete world-class? Not simply a physiological conundrum

Inter-individual variation in endurance performance capacity is a characteristic, not only of the general population, but also in trained athletes. The ability of sport scientists to predict which athletes amongst an elite group will become world-class is limited. We do not fully understand the interactions between biological factors, training, recovery and competitive performance. Assessment methods and interpretation of results do not take into account the facts that most research is not done on elite athletes and performances of world-class endurance athletes cannot be attributed to aerobic capacity alone. Many lines of evidence suggest that there is a limit to adaptation in aerobic capacity. Recent advances in molecular biology and genetics should be harnessed by exercise biologists in conjunction with previously used physiological, histological and biochemical techniques to study elite athletes and their responses to different training and recovery regimens. Technological advances should be harnessed to study world-class athletes to determine optimal training and competition strategies. In summary, it is likely that multiple factors are essential contributors to world-class endurance performance and that it is only by using a multidisciplinary approach that we will come closer to solving the conundrum: 'What makes an endurance athlete world class?'