Circulating microRNAs (c-miRNAs), plasma-based noncoding RNAs that control posttranscriptional gene expression, mediate processes that underlie phenotypical plasticity to exercise. The relationship and biological relevance between c-miRNA expression and variable dose exercise exposure remains uncertain. We hypothesized that certain c-miRNAs respond to changes in exercise intensity and/or duration in a dose-dependent fashion. Muscle release of such c-miRNAs may then deplete intracellular stores, thus facilitating gene reprogramming and exercise adaptation. To address these hypotheses, healthy men participated in variable intensity ( n = 12, 30 × 1 min at 6, 7, and 8 miles/h, order randomized) and variable duration ( n = 14, 7 × 1 mile/h for 30, 60, and 90 min, order randomized) treadmill-running protocols. Muscle-enriched c-miRNAs (i.e., miRNA-1 and miRNA-133a) and others with known relevance to exercise were measured before and after exercise. c-miRNA responses followed three profiles: 1) nonresponsive (miRNA-21 and miRNA-210), 2) responsive to exercise at some threshold but without dose dependence (miRNA-24 and miRNA-146a), and 3) responsive to exercise with dose dependence to increasing intensity (miRNA-1) or duration (miRNA-133a and miRNA-222). We also studied aerobic exercise-trained mice, comparing control, low-intensity (0.5 km/h), or high-intensity (1 km/h) treadmill-running protocols over 4 wk. In high- but not low-intensity-trained mice, we found increased plasma c-miR-133a along with decreased intracellular miRNA-133a and increased serum response factor, a known miR-133a target gene, in muscle. Characterization of c-miRNAs that are dose responsive to exercise in humans and mice supports the notion that they directly mediate physiological adaptation to exercise, potentially through depletion of intracellular stores of muscle-specific miRNAs. NEW & NOTEWORTHY In this study of humans and mice, we define circulating microRNAs in plasma that are dose responsive to exercise. Our data support the notion that these microRNAs mediate physiological adaptation to exercise potentially through depletion of intracellular stores of muscle-specific microRNAs and releasing their inhibitory effects on target gene expression.
Recent developments in evolutionary biology have conflicting implications for our understanding of the developmental bases of microevolutionary processes. On the one hand, Darwinian theory predicts that evolution occurs mostly gradually and incrementally through selection on small-scale, heritable changes in phenotype within populations. On the other hand, many discoveries in evolutionary developmental biology--quite a few based on comparisons of distantly related model organisms--suggest that relatively simple transformations of developmental pathways can lead to dramatic, rapid change in phenotype. Here I review the history of and bases for gradualist versus punctuationalist views from a developmental perspective, and propose a framework with which to reconcile them. Notably, while tinkering with developmental pathways can underlie large-scale transformations in body plan, the phenotypic effect of these changes is often modulated by the complexity of the genetic and epigenetic contexts in which they develop. Thus the phenotypic effects of mutations of potentially large effect can manifest themselves rapidly, but they are more likely to emerge more incrementally over evolutionary time via transitional forms as natural selection within populations acts on their expression. To test these hypotheses, and to better understand how developmental shifts underlie microevolutionary change, future research needs to be directed at understanding how complex developmental networks, both genetic and epigenetic, structure the phenotypic effects of particular mutations within populations of organisms.
The proximate mechanisms by which physical activity (PA) slows senescence and decreases morbidity and mortality have been extensively documented. However, we lack an ultimate, evolutionary explanation for why lifelong PA, particularly during middle and older age, promotes health. As the growing worldwide epidemic of physical inactivity accelerates the prevalence of noncommunicable diseases among aging populations, integrating evolutionary and biomedical perspectives can foster new insights into how and why lifelong PA helps preserve health and extend lifespans. Building on previous life-history research, we assess the evidence that humans were selected not just to live several decades after they cease reproducing but also to be moderately physically active during those postreproductive years. We next review the longstanding hypothesis that PA promotes health by allocating energy away from potentially harmful overinvestments in fat storage and reproductive tissues and propose the novel hypothesis that PA also stimulates energy allocation toward repair and maintenance processes. We hypothesize that selection in humans for lifelong PA, including during postreproductive years to provision offspring, promoted selection for both energy allocation pathways which synergistically slow senescence and reduce vulnerability to many forms of chronic diseases. As a result, extended human healthspans and lifespans are both a cause and an effect of habitual PA, helping explain why lack of lifelong PA in humans can increase disease risk and reduce longevity.
ABSTRACT Endurance runners are often advised to use 90 strides min−1, but how optimal is this stride frequency and why? Endurance runners are also often advised to maintain short strides and avoid landing with the feet too far in front of their hips or knees (colloquially termed ‘overstriding’), but how do different kinematic strategies for varying stride length at the same stride frequency affect economy and impact peaks? Linear mixed models were used to analyze repeated measures of stride frequency, the anteroposterior position of the foot at landing, V̇O2, lower extremity kinematics and vertical ground reaction forces in 14 runners who varied substantially in height and body mass and who were asked to run at 75, 80, 85, 90 and 95 strides min−1 at 3.0 m s−1. For every increase of 5 strides min−1, maximum hip flexor moments in the sagittal plane increased by 5.8% (P<0.0001), and the position of the foot at landing relative to the hip decreased by 5.9% (P=0.003). Higher magnitudes of posteriorly directed braking forces were associated with increases in foot landing position relative to the hip (P=0.0005) but not the knee (P=0.54); increases in foot landing position relative to the knee were associated with higher magnitudes (P<0.0001) and rates of loading (P=0.07) of the vertical ground reaction force impact peak. Finally, the mean metabolically optimal stride frequency was 84.8±3.6 strides min−1, with 50.4% of the variance explained by the trade-off between minimizing braking forces versus maximum hip flexor moments during swing. The results suggest that runners may benefit from a stride frequency of approximately 85 strides min−1 and by landing at the end of swing phase with a relatively vertical tibia.
