Modeling recent human evolution in mice by expression of a selected EDAR variant.

An adaptive variant of the human Ectodysplasin receptor, EDARV370A, is one of the strongest candidates of recent positive selection from genome-wide scans. We have modeled EDAR370A in mice and characterized its phenotype and evolutionary origins in humans. Our computational analysis suggests the allele arose in central China approximately 30,000 years ago. Although EDAR370A has been associated with increased scalp hair thickness and changed tooth morphology in humans, its direct biological significance and potential adaptive role remain unclear. We generated a knockin mouse model and find that, as in humans, hair thickness is increased in EDAR370A mice. We identify new biological targets affected by the mutation, including mammary and eccrine glands. Building on these results, we find that EDAR370A is associated with an increased number of active eccrine glands in the Han Chinese. This interdisciplinary approach yields unique insight into the generation of adaptive variation among modern humans.

Applying an evolutionary mismatch framework to understand disease susceptibility.

Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.

Foot callus thickness does not trade off protection for tactile sensitivity during walking.

Until relatively recently, humans, similar to other animals, were habitually barefoot. Therefore, the soles of our feet were the only direct contact between the body and the ground when walking. There is indirect evidence that footwear such as sandals and moccasins were first invented within the past 40 thousand years1, the oldest recovered footwear dates to eight thousand years ago2 and inexpensive shoes with cushioned heels were not developed until the Industrial Revolution3. Because calluses-thickened and hardened areas of the epidermal layer of the skin-are the evolutionary solution to protecting the foot, we wondered whether they differ from shoes in maintaining tactile sensitivity during walking, especially at initial foot contact, to improve safety on surfaces that can be slippery, abrasive or otherwise injurious or uncomfortable. Here we show that, as expected, people from Kenya and the United States who frequently walk barefoot have thicker and harder calluses than those who typically use footwear. However, in contrast to shoes, callus thickness does not trade-off protection, measured as hardness and stiffness, for the ability to perceive tactile stimuli at frequencies experienced during walking. Additionally, unlike cushioned footwear, callus thickness does not affect how hard the feet strike the ground during walking, as indicated by impact forces. Along with providing protection and comfort at the cost of tactile sensitivity, cushioned footwear also lowers rates of loading at impact but increases force impulses, with unknown effects on the skeleton that merit future study.

The active grandparent hypothesis: Physical activity and the evolution of extended human healthspans and lifespans.

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.

Biomechanical Tradeoffs in Foot Function From Variations in Shoe Design.

There is debate and confusion over how to evaluate the biomechanical effects of running shoe design. Here, we use an evolutionary perspective to analyze how key design features of running shoes alter the evolved biomechanics of the foot, creating a range of tradeoffs in force production and transmission that may affect performance and vulnerability to injury.

The effect of vertical load placement on metabolic rate during loaded walking in humans.

We examined the effects of vertical load placement on the metabolic cost of walking. Twelve healthy participants walked on a treadmill with 13.8 and 23.4 kg loads in both high and low vertical positions. Metabolic rate was measured using respirometry. While load position had no effect on the net metabolic rate for the 13.8 kg load, the net metabolic rate with the 23.4 kg load was significantly reduced by 4.3% in the high vertical load position compared to the low vertical load position. Loads carried higher on the trunk were also associated with increased forward trunk lean that reduced the load gravitational moment arm in the sagittal plane suggesting that reduction of fore-aft upper body torques is an energy-saving mechanism during loaded walking. Practitioner Summary: Load placement within a backpack affects the biomechanics of load carriage. We experimentally tested the metabolic cost of high and low load placement during walking and found the high position to be less costly with large loads. Loading high may be the optimal technique for carrying heavy backpacks.

Impact of meat and Lower Palaeolithic food processing techniques on chewing in humans.

The origins of the genus Homo are murky, but by H. erectus, bigger brains and bodies had evolved that, along with larger foraging ranges, would have increased the daily energetic requirements of hominins. Yet H. erectus differs from earlier hominins in having relatively smaller teeth, reduced chewing muscles, weaker maximum bite force capabilities, and a relatively smaller gut. This paradoxical combination of increased energy demands along with decreased masticatory and digestive capacities is hypothesized to have been made possible by adding meat to the diet, by mechanically processing food using stone tools, or by cooking. Cooking, however, was apparently uncommon until 500,000 years ago, and the effects of carnivory and Palaeolithic processing techniques on mastication are unknown. Here we report experiments that tested how Lower Palaeolithic processing technologies affect chewing force production and efficacy in humans consuming meat and underground storage organs (USOs). We find that if meat comprised one-third of the diet, the number of chewing cycles per year would have declined by nearly 2 million (a 13% reduction) and total masticatory force required would have declined by 15%. Furthermore, by simply slicing meat and pounding USOs, hominins would have improved their ability to chew meat into smaller particles by 41%, reduced the number of chews per year by another 5%, and decreased masticatory force requirements by an additional 12%. Although cooking has important benefits, it appears that selection for smaller masticatory features in Homo would have been initially made possible by the combination of using stone tools and eating meat.

Trunk muscle endurance, strength and flexibility in rural subsistence farmers and urban industrialized adults in western Kenya.

OBJECTIVES: High trunk muscle endurance, strength, and moderate flexibility reportedly help maintain musculoskeletal health, but there is evidence for tradeoffs among these variables as well as sex differences in trunk muscle endurance and strength. To test if these observations extend similarly to both men and women in nonindustrial and industrial environments, we investigated intra-individual associations and group and sex differences in trunk muscle endurance, strength, and flexibility among 74 (35 F, 39 M; age range: 18-61 years) adults from the same Kalenjin-speaking population in western Kenya. We specifically compared men and women from an urban community with professions that do not involve manual labor with rural subsistence farmers, including women who frequently carry heavy loads. METHODS: Trunk muscle endurance, strength, and flexibility were measured with exercise tests and electromyography (EMG). RESULTS: We found a positive correlation between trunk extensor strength and endurance (R = .271, p ≤ .05) and no associations between strength or endurance and flexibility. Rural women had higher trunk extensor and flexor endurance, EMG-determined longissimus lumborum endurance, and trunk extensor strength than urban women (all p ≤ .05). Rural women had higher trunk extensor and flexor endurance than rural men (both p ≤ .05). Urban women had lower trunk flexor and extensor endurance than urban men (both p ≤ .01). CONCLUSIONS: High levels of physical activity among nonindustrial subsistence farmers, particularly head carrying among women, appear to be associated with high trunk muscle endurance and strength, which may have important benefits for helping maintain musculoskeletal health.

Selection of endurance capabilities and the trade-off between pressure and volume in the evolution of the human heart.

Chimpanzees and gorillas, when not inactive, engage primarily in short bursts of resistance physical activity (RPA), such as climbing and fighting, that creates pressure stress on the cardiovascular system. In contrast, to initially hunt and gather and later to farm, it is thought that preindustrial human survival was dependent on lifelong moderate-intensity endurance physical activity (EPA), which creates a cardiovascular volume stress. Although derived musculoskeletal and thermoregulatory adaptations for EPA in humans have been documented, it is unknown if selection acted similarly on the heart. To test this hypothesis, we compared left ventricular (LV) structure and function across semiwild sanctuary chimpanzees, gorillas, and a sample of humans exposed to markedly different physical activity patterns. We show the human LV possesses derived features that help augment cardiac output (CO) thereby enabling EPA. However, the human LV also demonstrates phenotypic plasticity and, hence, variability, across a wide range of habitual physical activity. We show that the human LV's propensity to remodel differentially in response to chronic pressure or volume stimuli associated with intense RPA and EPA as well as physical inactivity represents an evolutionary trade-off with potential implications for contemporary cardiovascular health. Specifically, the human LV trades off pressure adaptations for volume capabilities and converges on a chimpanzee-like phenotype in response to physical inactivity or sustained pressure loading. Consequently, the derived LV and lifelong low blood pressure (BP) appear to be partly sustained by regular moderate-intensity EPA whose decline in postindustrial societies likely contributes to the modern epidemic of hypertensive heart disease.

Characteristics and Future Direction of Tibialis Posterior Tendinopathy Research: A Scoping Review.

Background and Objectives: Tibialis posterior tendon pathologies have been traditionally categorized into different stages of posterior tibial tendon dysfunction (PTTD), or adult acquired flatfoot deformity (AAFD), and more recently to progressive collapsing foot deformity (PCFD). The purpose of this scoping review is to synthesize and characterize literature on early stages of PTTD (previously known as Stage I and II), which we will describe as tibialis posterior tendinopathy (TPT). We aim to identify what is known about TPT, identify gaps in knowledge on the topics of TPT, and propose future research direction. Materials and Methods: We included 44 studies and categorized them into epidemiology, diagnosis, evaluation, biomechanics outcome measure, imaging, and nonsurgical treatment. Results: A majority of studies (86.4%, 38 of 44 studies) recruited patients with mean or median ages greater than 40. For studies that reported body mass index (BMI) of the patients, 81.5% had mean or median BMI meeting criteria for being overweight. All but two papers described study populations as predominantly or entirely female gender. Biomechanical studies characterized findings associated with TPT to include increased forefoot abduction and rearfoot eversion during gait cycle, weak hip and ankle performance, and poor balance. Research on non-surgical treatment focused on orthotics with evidence mostly limited to observational studies. The optimal exercise regimen for the management of TPT remains unclear due to the limited number of high-quality studies. Conclusions: More epidemiological studies from diverse patient populations are necessary to better understand prevalence, incidence, and risk factors for TPT. The lack of high-quality studies investigating nonsurgical treatment options is concerning because, regardless of coexisting foot deformity, the initial treatment for TPT is typically conservative. Additional studies comparing various exercise programs may help identify optimal exercise therapy, and investigation into further nonsurgical treatments is needed to optimize the management for TPT.

The extensibility of the plantar fascia influences the windlass mechanism during human running.

The arch of the human foot is unique among hominins as it is compliant at ground contact but sufficiently stiff to enable push-off. These behaviours are partly facilitated by the ligamentous plantar fascia whose role is central to two mechanisms. The ideal windlass mechanism assumes that the plantar fascia has a nearly constant length to directly couple toe dorsiflexion with a change in arch shape. However, the plantar fascia also stretches and then shortens throughout gait as the arch-spring stores and releases elastic energy. We aimed to understand how the extensible plantar fascia could behave as an ideal windlass when it has been shown to strain throughout gait, potentially compromising the one-to-one coupling between toe arc length and arch length. We measured foot bone motion and plantar fascia elongation using high-speed X-ray during running. We discovered that toe plantarflexion delays plantar fascia stretching at foot strike, which probably modifies the distribution of the load through other arch tissues. Through a pure windlass effect in propulsion, a quasi-isometric plantar fascia's shortening is delayed to later in stance. The plantar fascia then shortens concurrently to the windlass mechanism, likely enhancing arch recoil at push-off.

A systematic review of adherence to physical activity interventions in individuals with type 2 diabetes.

Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.

The human foot functions like a spring of adjustable stiffness during running.

Like other animals, humans use their legs like springs to save energy during running. One potential contributor to leg stiffness in humans is the longitudinal arch (LA) of the foot. Studies of cadaveric feet have demonstrated that the LA can function like a spring, but it is unknown whether humans can adjust LA stiffness in coordination with more proximal joints to help control leg stiffness during running. Here, we used 3D motion capture to record 27 adult participants running on a forceplate-instrumented treadmill, and calculated LA stiffness using beam bending and midfoot kinematics models of the foot. Because changing stride frequency causes humans to adjust overall leg stiffness, we had participants run at their preferred frequency and frequencies 35% above and 20% below preferred frequency to test for similar adjustments in the LA. Regardless of which foot model we used, we found that participants increased LA quasi-stiffness significantly between low and high frequency runs, mirroring changes at the ankle, knee and leg overall. However, among foot models, we found that the model incorporating triceps surae force into bending force on the foot produced unrealistically high LA work estimates, leading us to discourage this modeling approach. Additionally, we found that there was not a consistent correlation between LA height and quasi-stiffness values among the participants, indicating that static LA height measurements are not good predictors of dynamic function. Overall, our findings support the hypothesis that humans dynamically adjust LA stiffness during running in concert with other structures of the leg.

Stepping Back to Minimal Footwear: Applications Across the Lifespan.

Minimal footwear has existed for tens of thousands of years and was originally designed to protect the sole of the foot. Over the past 50 yr, most footwear has become increasingly more cushioned and supportive. Here, we review evidence that minimal shoes are a better match to our feet, which may result in a lower risk of musculoskeletal injury.

Shorter distal forelimbs benefit bipedal walking and running mechanics: Implications for hominin forelimb evolution.

OBJECTIVES: Brachial index is a skeletal ratio that describes the relative length of the distal forelimb. Over the course of hominin evolution, a shift toward smaller brachial indices occurred. First, Pleistocene australopiths yield values between extant chimpanzees and humans, with further evolution in Pliocene Homo to the modern human range. We hypothesized that shorter distal forelimbs benefit walking and running performance, notably elbow and shoulder joint torques, and predicted that the benefit would be greater in running compared to walking. MATERIALS AND METHODS: We tested our hypothesis in a modern human sample walking and running while carrying hand weights, which increase the inertia (mass and effective length) of the distal forelimb, simulating a larger brachial index. RESULTS: We found longer distal forelimbs and the added mass increased elbow muscle torque by 98% while walking and 70% in running, confirming our hypothesis that shorter distal forelimbs benefit walking and running performance. Shoulder muscle torque similarly increased in both gaits with the addition of hand weights due to elongation of the effective forelimb length. Normalized elbow torque, which accounted for the effect on shoulder torque caused by the experimental manipulation, increased by 16% while walking but 52% while running, indicating that shorter distal forelimbs provide a greater benefit for running by approximately three-fold. DISCUSSION: Selection for economical bipedal walking in Australopithecus and endurance running in Homo likely contributed to the shift toward relatively smaller distal forelimbs across hominin evolution, with modern human proportions attained in Pleistocene Homo erectus and retained in later species.

Neuromechanical linkage between the head and forearm during running.

OBJECTIVES: The main objective was to test the hypothesis of a neuromechanical link in humans between the head and forearm during running mediated by the biceps brachii and superior trapezius muscles. We hypothesized that this linkage helps stabilize the head and combats rapid forward pitching during running which may interfere with gaze stability. MATERIALS AND METHODS: Thirteen human participants walked and ran on a treadmill while motion capture recorded body segment kinematics and electromyographic sensors recorded muscle activation. To test perturbations to the linkage system we compared participants running normally as well as with added mass to the face and the hand. RESULTS: The results confirm the presence of a neuromechanical linkage between the head and forearm mediated by the biceps and superior trapezius during running but not during walking. In running, the biceps and superior trapezius activations were temporally linked during the stride cycle, and adding mass to either the head or hand increased activation in both muscles, consistent with our hypothesis. During walking the forces acting on the body segments and muscle activation levels were much smaller than during running, indicating no need for a linkage to keep the head and gaze stable. DISCUSSION: The results suggest that the evolution of long distance running in early Homo may have favored selection for reduced rotational inertia of both the head and forearm through synergistic muscle activation, contributing to the transition from australopith head and forelimb morphology to the more human-like form of Homo erectus. Selective pressures from the evolution of bipedal walking were likely much smaller, but may explain in part the intermediate form of the australopith scapula between that of extant apes and humans.

Physical and geometric constraints shape the labyrinth-like nasal cavity.

The nasal cavity is a vital component of the respiratory system that heats and humidifies inhaled air in all vertebrates. Despite this common function, the shapes of nasal cavities vary widely across animals. To understand this variability, we here connect nasal geometry to its function by theoretically studying the airflow and the associated scalar exchange that describes heating and humidification. We find that optimal geometries, which have minimal resistance for a given exchange efficiency, have a constant gap width between their side walls, while their overall shape can adhere to the geometric constraints imposed by the head. Our theory explains the geometric variations of natural nasal cavities quantitatively, and we hypothesize that the trade-off between high exchange efficiency and low resistance to airflow is the main driving force shaping the nasal cavity. Our model further explains why humans, whose nasal cavities evolved to be smaller than expected for their size, become obligate oral breathers in aerobically challenging situations.

Evolutionary anatomy of the plantar aponeurosis in primates, including humans.

The plantar aponeurosis in the human foot has been extensively studied and thoroughly described, in part, because of the incidence of plantar fasciitis in humans. It is commonly assumed that the human plantar aponeurosis is a unique adaptation to bipedalism that evolved in concert with the longitudinal arch. However, the comparative anatomy of the plantar aponeurosis is poorly known in most mammals, even among non-human primates, hindering efforts to understand its function. Here, we review previous anatomical descriptions of 40 primate species and use phylogenetic comparative methods to reconstruct the evolution of the plantar aponeurosis and its relationship to the plantaris muscle in primates. Ancestral state reconstructions suggest that the overall organization of the human plantar aponeurosis is shared with chimpanzees and that a similar anatomical configuration evolved independently in different primate clades as an adaptation to terrestrial locomotion. The presence of a plantar aponeurosis with clearly developed lateral and central bands in the African apes suggests that this structure is not prohibitive to suspensory locomotion and that these species possess versatile feet adapted for both terrestrial and arboreal locomotion. This plantar aponeurosis configuration would have been advantageous in enhancing foot stiffness for bipedal locomotion in the earliest hominins, prior to the evolution of a longitudinal arch. Hominins may have subsequently evolved thicker and stiffer plantar aponeuroses alongside the arch to enable a windlass mechanism and elastic energy storage for bipedal walking and running, although this idea requires further testing.

WEIRD bodies: mismatch, medicine and missing diversity.

Despite recent rapid advances in medical knowledge that have improved survival, conventional medical science's understanding of human health and disease relies heavily on people of European descent living in contemporary urban industrialized environments. Given that modern conditions in high-income countries differ widely in terms of lifestyle and exposures compared to those experienced by billions of people and all our ancestors over several hundred thousand years, this narrow approach to the human body and health is very limiting. We argue that preventing and treating chronic diseases of aging and other mismatch diseases will require both expanding study design to sample diverse populations and contexts, and fully incorporating evolutionary perspectives. In this paper, we first assess the extent of biased representation of industrialized populations in high profile, international biomedical journals, then compare patterns of morbidity and health across world regions. We also compare demographic rates and the force of selection between subsistence and industrialized populations to reflect on the changes in how selection operates on fertility and survivorship across the lifespan. We argue that, contrary to simplistic misguided solutions like the PaleoDiet, the hypothesis of evolutionary mismatch needs critical consideration of population history, evolutionary biology and evolved reaction norms to prevent and treat diseases. We highlight the critical value of broader sampling by considering the effects of three key exposures that have radically changed over the past century in many parts of the world-pathogen burden, reproductive effort and physical activity-on autoimmune, cardiometabolic and other mismatch diseases.