The ability of the nervous system to sense cellular stress and coordinate protein homeostasis is essential for organismal health. Unfortunately, stress responses that mitigate disturbances in proteostasis, such as the unfolded protein response of the endoplasmic reticulum (UPRER), become defunct with age. In this work, we expressed the constitutively active UPRERtranscription factor, XBP-1s, in a subset of astrocyte-like glia, which extended the life span in
Considerable progress has been made in understanding the physiological basis for variation in the life‐history patterns of animals, particularly with regard to the roles of oxidative stress and hormonal regulation. However, an underappreciated and understudied area that could play a role in mediating inter‐ and intraspecific variation of life history is endoplasmic reticulum (ER) stress, and the resulting unfolded protein response (UPRER). ER stress response and the UPRERmaintain proteostasis in cells by reducing the intracellular load of secretory proteins and enhancing protein folding capacity or initiating apoptosis in cells that cannot recover. Proper modulation of the ER stress response and execution of the UPRERallow animals to respond to intracellular and extracellular stressors and adapt to constantly changing environments. ER stress responses are heritable and there is considerable individual variation in UPRERphenotype in animals, suggesting that ER stress and UPRERphenotype can be subjected to natural selection. The variation in UPRERphenotype presumably reflects the way animals respond to ER stress and environmental challenges. Most of what we know about ER stress and the UPRERin animals has either come from biomedical studies using cell culture or from experiments involving conventional laboratory or agriculturally important models that exhibit limited genetic diversity. Furthermore, these studies involve the assessment of experimentally induced qualitative changes in gene expression as opposed to the quantitative variations that occur in naturally existing populations. Almost all of these studies were conducted in controlled settings that are often quite different from the conditions animals experience in nature. Herein, we review studies that investigated ER stress and the UPRERin relation to key life‐history traits including growth and development, reproduction, bioenergetics and physical performance, and ageing and senescence. We then ask if these studies can inform us about the role of ER stress and the UPRERin mediating the aforementioned life‐history traits in free‐living animals. We propose that there is a need to conduct experiments pertaining to ER stress and the UPRERin ecologically relevant settings, to characterize variation in ER stress and the UPRERin free‐living animals, and to relate the observed variation to key life‐history traits. We urge others to integrate multiple physiological systems and investigate how interactions between ER stress and oxidative stress shape life‐history trade‐offs in free‐living animals.
more » « less- NSF-PAR ID:
- 10382044
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Biological Reviews
- Volume:
- 96
- Issue:
- 2
- ISSN:
- 1464-7931
- Page Range / eLocation ID:
- p. 541-556
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
more » « less
Caenorhabditis elegans . Glial XBP-1s initiated a robust cell nonautonomous activation of the UPRERin distal cells and rendered animals more resistant to protein aggregation and chronic ER stress. Mutants deficient in neuropeptide processing and secretion suppressed glial cell nonautonomous induction of the UPRERand life-span extension. Thus, astrocyte-like glial cells play a role in regulating organismal ER stress resistance and longevity. -
more » « less
Abstract Long‐term studies of wild animals provide the opportunity to investigate how phenotypic plasticity is used to cope with environmental fluctuations and how the relationships between phenotypes and fitness can be dependent upon the ecological context.
Many previous studies have only investigated life‐history plasticity in response to changes in temperature, yet wild animals often experience multiple environmental fluctuations simultaneously. This requires field experiments to decouple which ecological factor induces plasticity in fitness‐relevant traits to better understand their population‐level responses to those environmental fluctuations.
For the past 32 years, we have conducted a long‐term integrative study of individually marked North American red squirrels
Tamiasciurus hudsonicus Erxleben in the Yukon, Canada. We have used multi‐year field experiments to examine the physiological and life‐history responses of individual red squirrels to fluctuations in food abundance and conspecific density.Our long‐term observational study and field experiments show that squirrels can anticipate increases in food availability and density, thereby decoupling the usual pattern where animals respond to, rather than anticipate, an ecological change.
As in many other study systems, ecological factors that can induce plasticity (such as food and density) covary. However, our field experiments that manipulate food availability and social cues of density (frequency of territorial vocalizations) indicate that increases in social (acoustic) cues of density in the absence of additional food can induce similar life‐history plasticity, as does experimental food supplementation.
Changes in the levels of metabolic hormones (glucocorticoids) in response to variation in food and density are one mechanism that seems to induce this adaptive life‐history plasticity.
Although we have not yet investigated the energetic response of squirrels to elevated density or its association with life‐history plasticity, energetics research in red squirrels has overturned several standard pillars of knowledge in physiological ecology.
We show how a tractable model species combined with integrative studies can reveal how animals cope with resource fluctuations through life‐history plasticity.
-
null (Ed.)Abstract For over three decades, scientists have conducted heat-stress experiments to predict how coral will respond to ocean warming due to global climate change. However, there are often conflicting results in the literature that are difficult to resolve, which we hypothesize are a result of unintended biases, variation in experimental design, and underreporting of critical methodological information. Here, we reviewed 255 coral heat-stress experiments to (1) document where and when they were conducted and on which species, (2) assess variability in experimental design, and (3) quantify the diversity of response variables measured. First, we found that two-thirds of studies were conducted in only three countries, three coral species were more heavily studied than others, and only 4% of studies focused on earlier life stages. Second, slightly more than half of all heat-stress exposures were less than 8 d in duration, only 17% of experiments fed corals, and experimental conditions varied widely, including the level and rate of temperature increase, light intensity, number of genets used, and the length of acclimation period. In addition, 95%, 55%, and > 35% of studies did not report tank flow conditions, light–dark cycle used, or the date of the experiment, respectively. Finally, we found that 21% of experiments did not measure any bleaching phenotype traits, 77% did not identify the Symbiodiniaceae endosymbiont, and the contribution of the coral host in the physiological response to heat-stress was often not investigated. This review highlights geographic, taxonomic, and heat-stress duration biases in our understanding of coral bleaching, and large variability in the reporting and design of heat-stress experiments that could account for some of the discrepancies in the literature. Development of some best practice recommendations for coral bleaching experiments could improve cross-studies comparisons and increase the efficiency of coral bleaching research at a time when it is needed most.more » « less
-
We treated potato (Solanum tuberosum L.) plantlets with TM and performed gene expression studies to identify genome-wide changes associated with endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). An extensive network of responses was identified, including chromatin remodeling, transcriptional reprogramming, as well as changes in the structural components of the endomembrane network system. Limited genome-wide changes in alternative RNA splicing patterns of protein-coding transcripts were also discovered. Significant changes in RNA metabolism, components of the translation machinery, as well as factors involved in protein folding and maturation occurred, which included a broader set of genes than expected based on Arabidopsis research. Antioxidant defenses and oxygen metabolic enzymes are differentially regulated, which is expected of cells that may be experiencing oxidative stress or adapting to protect proteins from oxidation. Surges in protein kinase expression indicated early signal transduction events. This study shows early genomic responses including an array of differentially expressed genes that have not been reported in Arabidopsis. These data describe novel ER stress responses in a solanaceous host.more » « less
-
Endoplasmic reticulum (ER) stress has been causatively linked to the onset of various pathologies. However, if and how inherent variations in the resulting unfolded protein response (UPR) affect the predisposition to ER stress-associated metabolic conditions remains to be established. By using genetically diverse deer mice (Peromyscus maniculatus) as a model, we show that the profile of tunicamycin-induced UPR in fibroblasts isolated at puberty varies between individuals and predicts deregulation of lipid metabolism and diet-induced hepatic steatosis later in life. Among the different UPR targets tested, CHOP more consistently predicted elevated plasma cholesterol and hepatic steatosis. Compared to baseline levels or inducibility, the maximal intensity of the UPR following stimulation best predicts the onset of pathology. Differences in the expression profile of the UPR recorded in cells from different populations of deer mice correlate with the varying response to ER stress in altitude adaptation. Our data suggest that the response to ER stress in cultured cells varies among individuals and its profile early in life may predict the onset of ER stress-associated disease in the elderly.more » « less
