skip to main content

Title: Defining biological stress and stress responses based on principles of physics

Stress represents a multi‐faceted force that is central for the evolution of life. Organisms evolve while adapting to stress and stressful contexts often represent selective bottlenecks. To understand stress effects on biological systems and corresponding coping strategies it is imperative to properly define stress and the resulting strain that triggers compensatory responses in cells and organisms. Here I am deriving such definitions for biological systems based on principles that are established in physics. The relationship between homeostasis of critical biological variables, the elastic limit, the cellular stress response (CSR), cellular homeostasis response (CHR), system dysregulation, and the breaking point (death of the system) is outlined. Dysregulation of homeostatic set‐points of biological variables perturbs the functional properties of the system, shifting them out of the evolutionarily optimized range. Such shifts are accompanied by elevated rates of macromolecular damage, which represents a nonspecific signal for induction of a universal response, the CSR. The CSR complements the CHR in re‐establishing homeostasis of the system as a whole. Moreover, the CSR is essential for coping with suboptimal conditions while the system is in a dysregulated state and for removing excessive damage that accumulates during such periods. The extreme complexity of biological systems and their emergent properties often necessitate monitoring stress effects on many biological variables simultaneously to properly deduce stress effects on the system as a whole. Therefore, increased utilization of systems biology (omics) approaches for characterizing cellular and organismal stress responses facilitates the reductionist dissection of biological stress response mechanisms.

more » « less
Award ID(s):
Author(s) / Creator(s):
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Journal of Experimental Zoology Part A: Ecological and Integrative Physiology
Page Range / eLocation ID:
p. 350-358
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    The cellular stress response (CSR) is pervasive to all domains of life. It has shaped the interaction between organisms and their environment since the origin of the first cell. Although the CSR has been subject to a myriad of nuanced modifications in the various branches of life present today, its core features remain preserved. The scientific literature covering the CSR is enormous and the broad scope of this brief overview was challenging. However, it is critical to conceptually understand how cells respond to stress in a holistic sense and to point out how fundamental aspects of the CSR framework are integrated. It was necessary to be extremely selective and not feasible to even mention many interesting and important developments in this expansive field. The purpose of this overview is to sketch out general and emerging CSR concepts with an emphasis on the initial cellular strain resulting from stress (macromolecular damage) and the evolutionarily most highly conserved elements of the CSR. Examples emphasize fish and aquatic invertebrates to highlight what is known in organisms beyond mammals, yeast, and other common models. Nonetheless, select pioneering studies using canonical models are also considered and the concepts discussed are applicable to all cells. More detail on important aspects of the CSR in aquatic animals is provided in the accompanying articles of this special issue.

    more » « less
  2. Abstract

    Salinity stress occurs when salt concentration in the environment changes rapidly, for example because of tidal water flow, rainstorms, drought, or evaporation from small bodies of water. However, gradual changes in salt concentration can also cause osmotic stress in aquatic habitats if levels breach thresholds that reduce the fitness of resident organisms. The latter scenario is exemplified by climate change driven salinization of estuaries and by dilution of ocean surface salinity through changes in the water cycle. In this review, we discuss how fish employ the evolutionarily conserved cellular stress response (CSR) to cope with these different forms of salinity stress. Macromolecular damage is identified as the cause of impaired physiological performance during salinity stress and serves as the signal for inducing a CSR. Basic aspects of the CSR have been observed in fish exposed to salinity stress, including repair and protection of cellular macromolecules, reallocation of energy, cell cycle arrest, and in severe cases, programmed cell death. Osmosensing and signal transduction events that regulate these aspects of the CSR provide a link between environmental salinity and adaptive physiological change required for survival. The CSR has evolved to broaden the range of salinities tolerated by certain euryhaline fish species, but is constrained in stenohaline species that are sensitive to changes in environmental salinity. Knowledge of how the CSR diverges between euryhaline and stenohaline fish enables understanding of physiological mechanisms that underlie salt tolerance and facilitates predictions as to the relative vulnerabilities of different fish species to a rapidly changing hydrosphere.

    more » « less
  3. Abstract As part of mitonuclear communication, retrograde and anterograde signaling helps maintain homeostasis under basal conditions. Basal conditions, however, vary across phylogeny. At the cell-level, some mitonuclear retrograde responses can be quantified by measuring the constitutive components of oxidative stress, the balance between reactive oxygen species (ROS) and antioxidants. ROS are metabolic by-products produced by the mitochondria that can damage macromolecules by structurally altering proteins and inducing mutations in DNA, among other processes. To combat accumulating damage, organisms have evolved endogenous antioxidants and can consume exogenous antioxidants to sequester ROS before they cause cellular damage. ROS are also considered to be regulated through a retrograde signaling cascade from the mitochondria to the nucleus. These cellular pathways may have implications at the whole-animal level as well. For example, birds have higher basal metabolic rates, higher blood glucose concentration, and longer lifespans than similar sized mammals, however, the literature is divergent on whether oxidative stress is higher in birds compared with mammals. Herein, we collected literature values for whole-animal metabolism of birds and mammals. Then, we collected cellular metabolic rate data from primary fibroblast cells isolated from birds and mammals and we collected blood from a phylogenetically diverse group of birds and mammals housed at zoos and measured several parameters of oxidative stress. Additionally, we reviewed the literature on basal-level oxidative stress parameters between mammals and birds. We found that mass-specific metabolic rates were higher in birds compared with mammals. Our laboratory results suggest that cellular basal metabolism, total antioxidant capacity, circulating lipid damage, and catalase activity were significantly lower in birds compared with mammals. We found no body-size correlation on cellular metabolism or oxidative stress. We also found that most oxidative stress parameters significantly correlate with increasing age in mammals, but not in birds; and that correlations with reported maximum lifespans show different results compared with correlations with known aged birds. Our literature review revealed that basal levels of oxidative stress measurements for birds were rare, which made it difficult to draw conclusions. 
    more » « less
  4. Summary

    Stress is ubiquitous and disrupts homeostasis, leading to damage, decreased fitness, and even death. Like other organisms, mycorrhizal fungi evolved mechanisms for stress tolerance that allow them to persist or even thrive under environmental stress. Such mechanisms can also protect their obligate plant partners, contributing to their health and survival under hostile conditions. Here we review the effects of stress and mechanisms of stress response in mycorrhizal fungi. We cover molecular and cellular aspects of stress and how stress impacts individual fitness, physiology, growth, reproduction, and interactions with plant partners, along with how some fungi evolved to tolerate hostile environmental conditions. We also address how stress and stress tolerance can lead to adaptation and have cascading effects on population‐ and community‐level diversity. We argue that mycorrhizal fungal stress tolerance can strongly shape not only fungal and plant physiology, but also their ecology and evolution. We conclude by pointing out knowledge gaps and important future research directions required for both fully understanding stress tolerance in the mycorrhizal context and addressing ongoing environmental change.

    more » « less
  5. Abstract

    Vertebrates respond to a diversity of stressors by rapidly elevating glucocorticoid (GC) levels. The changes in physiology and behavior triggered by this response can be crucial for surviving a variety of challenges. Yet the same process that is invaluable in coping with immediate threats can also impose substantial damage over time. In addition to the pathological effects of long-term exposure to stress hormones, even relatively brief elevations can impair the expression of a variety of behaviors and physiological processes central to fitness, including sexual behavior, parental behavior, and immune function. Therefore, the ability to rapidly and effectively terminate the short-term response to stress may be fundamental to surviving and reproducing in dynamic environments. Here we review the evidence that variation in the ability to terminate the stress response through negative feedback is an important component of stress coping capacity. We suggest that coping capacity may also be influenced by variation in the dynamic regulation of GCs—specifically, the ability to rapidly turn on and off the stress response. Most tests of the fitness effects of these traits to date have focused on organisms experiencing severe or prolonged stressors. Here we use data collected from a long-term study of tree swallows (Tachycineta bicolor) to test whether variation in negative feedback, or other measures of GC regulation, predict components of fitness in non-chronically stressed populations. We find relatively consistent, but generally weak relationships between different fitness components and the strength of negative feedback. Reproductive success was highest in individuals that both mounted a robust stress response and had strong negative feedback. We did not see consistent evidence of a relationship between negative feedback and adult or nestling survival: negative feedback was retained in the best supported models of nestling and adult survival, but in two of three survival-related analyses the intercept-only model received only slightly less support. Both negative feedback and stress-induced GC levels—but not baseline GCs—were individually repeatable. These measures of GC activity did not consistently covary across ages and life history stages, indicating that they are independently regulated. Overall, the patterns seen here are consistent with the predictions that negative feedback—and the dynamic regulation of GCs—are important components of stress coping capacity, but that the fitness benefits of having strong negative feedback during the reproductive period are likely to manifest primarily in individuals exposed to chronic or repeated stressors.

    more » « less