Physiology in Perspective: In a World of Social Distancing

Humans are a social species and we have evolved to help each other in troubled times and work together toward common goals. There is no better example of the importance of working together than our shared goal to limit the impact of the COVID-19 virus. Ironically, we must do this via social distancing, thereby limiting contact between and among humans. In doing this, our essential strategy is to mitigate the rate of infection of the coronavirus, flatten the pandemic curve, and stay within our local capacities for healthcare. However, limiting person-to-person contact goes against our basic human nature. We have taken for granted our daily lives of going out in crowds to restaurants, to stores, and riding on airplanes or buses. Social interaction is part of our daily lives, and, at least temporarily, we will miss this social contact. Yet, we can still work together through various forms of indirect contact, mostly via electronic communication. The lack of direct social contact will not deter the sharing of scientific discoveries. Yes, scientific meetings such as Experimental Biology have been canceled, but scientists can still communicate with each other and with the outside world. Already, we are gaining insight into the underlying pathophysiological mechanisms that lead to lung injury and respiratory complications in COVID-19 infections. Still unresolved is why the pathophysiological impact is so much more pronounced in our elderly population. Hopefully, the COVID-19 pandemic will be short-lived and stay within our healthcare capacity. Importantly, our national/international response to the coronavirus emphasizes the need for increasing basic biomedical research and integrating this research into an appropriate immediate response and planning for the future.

Almost all organisms that comprise the tree of life are ectotherms, i.e., their body temperature tracks the environmental temperature. Among this vast diversity of life, humans, like other mammals, have inherited a relatively rare metabolism, where food is burned, in part, to maintain body temperature (endothermy). The evolutionary selective pressures and trade-offs, both in terms of fitness of the lineage and in terms of the cellular and molecular underpinnings of thermogenesis, have long been a subject of interest and speculation, but remain incompletely understood. In her review (2), Farmer discusses the larger view of convergent evolution of parental care as a lens through which the striking adaptations of endothermy can be viewed. She presents this view in the context of some new discoveries, including the facultative endothermy of tegu lizards—a lineage with extraordinary parental care behaviors. Convergence is an important evolutionary phenomenon because it is one of the strongest lines of evidence for the adaptive significance of a trait. Although, like endothermy, parental care behaviors are relatively rare, they represent one of the most impressive examples of convergent evolution, and this behavior serves, time and again, and in groups as different as plants, insects, and humans, to confer on parents the ability to control the developmental temperature of their offspring. Understanding the history that gave rise to our own unique metabolism should help clarify the genetic and physiological architecture and mechanisms that underpin human endothermy, and how they may intertwine with the evolution of the limbic system and its neural and hormonal controls of both behavior and metabolism.

The participation of women in physically strenuous athletic and occupational tasks has increased substantially in the past decade. Historically, women were often excluded from many athletic competitions due to assumptions that their ability to thermoregulate was impaired relative to men. More recent work confirms certain differences between men and women in physiological mechanisms of thermoregulation, but no major differences that put women at a disadvantage for thermoregulation during exercise in the heat. In their review (5), Yanovich and colleagues discuss exercise and heat stress in women. Female sex steroids have influences on physiological thermoregulatory processes that could impact physical performance in the heat. For example, cutaneous vasodilation and sweating are altered by estrogen and progesterone. Vasodilation in general is augmented in the presence of estrogen, in part via increased activity of β-adrenergic receptors. Although this is helpful for tissue perfusion and heat dissipation, the systemic vasodilation also increases the risk and incidence of orthostatic intolerance, which is also exacerbated by heat exposure. Women tend to sweat less, which has been seen as a disadvantage in endurance events in the heat, but also tend to sweat more efficiently, which likely allows for less wasted sweat, particularly in hot environments. Interestingly, behavioral strategies for endurance events seem to be stronger in women, such that women put themselves at less risk for a heat illness event by planning better to prevent it.

Modern lifestyles include longer periods of daily food intake and shorter fasting periods, which are directly associated with the global epidemic of obesity and metabolic diseases. Therefore, it is becoming increasingly more important to uncover novel, yet feasible, weight-management approaches. Recently, accumulating studies demonstrated that limiting the caloric intake duration to a shorter time window, such as intermittent fasting (IF), without changing the diet quantity or quality has significant metabolic benefits. These observations highlight the importance of not only “what/how much” but also “when/how often” we eat to sustain energy homeostasis and metabolic health. In their review (3), Lee et al. discuss basic animal and human research exploring the physiology of IF. Due to its simple and practical protocol, IF or other similar diet regimens have gained significant attention not only from the general population but also from many health researchers. However, although numerous animal studies have reported positive health benefits of IF, its feasibility and efficacy in clinical settings remain controversial. Importantly, since IF has systemic effects, it is important to thoroughly investigate the tissue-specific changes in animal models to identify underlying mechanisms of IF effects and to evaluate any potential adverse effects of IF in humans.

Striking functional differences have evolved in sperm due to diverse fertilizing environments. Marine invertebrates and fish spawn their gametes into sea or fresh water, which can vary in composition, hydrodynamics, and temperature. Mammals release their sperm into the female genital tract, which differing species have evolved into a variety of topologies with distinct cell components that determine the composition and physical properties of the fluid where sperm must travel to find the egg. In their review (1), Darszon and colleagues discuss similarities and differences in sperm strategies. Sperm from different species use a variety of signaling pathways to communicate as they search for the female gamete. We do not yet understand the functional implications of vesicles from the epididymis, prostate, and female genital tract that can transfer different proteins, RNAs, and metabolites to sperm during their journey toward the egg, and even transmit information beyond fertilization. Species preservation depends on the success of fertilization, and experiments addressing questions arising from comparative genomic analysis in different species are necessary to better understand sperm physiology.

Muscle is conventionally viewed as a motor that converts chemical to kinetic energy in series with a passive spring. However, new insights emerge when muscle is viewed as a composite material, like rubber, whose elastic properties change with activation. Titin is the largest known protein and the third most abundant protein in muscle. It has been viewed as contributing to sarcomere structure as a scaffold for other proteins, as well as contributing to muscle passive tension. In his review (4), Nishikawa discusses titin’s contribution to active muscle contraction. Experimental evidence demonstrates that titin stiffness changes on muscle activation. Calcium-dependent binding of titin to actin changes titin length and stiffness. These changes help to explain muscle properties, including force enhancement after stretch and force depression after shortening. The muscle properties provide adaptive responses to unexpected perturbations of locomotion and other movements, properties that are long known but unexplained by current theories. Incorporating a tunable titin spring in muscle models contributes to the understanding of the roles that muscle plays in coordinating and controlling human movement. These concepts have inspired the design of control algorithms for powered prosthetic devices and exoskeletons.