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  1. Abstract

    DNA methylation-based biomarkers of aging have been developed for humans and many other mammals and could be used to assess how stress factors impact aging. Deer mice (Peromyscus) are long-living rodents that have emerged as an informative model to study aging, adaptation to extreme environments, and monogamous behavior. In the present study, we have undertaken an exhaustive, genome-wide analysis of DNA methylation inPeromyscus, spanning different species, stocks, sexes, tissues, and age cohorts. We describe DNA methylation-based estimators of age for different species of deer mice based on novel DNA methylation data generated on highly conserved mammalian CpGs measured with a custom array. The multi-tissue epigenetic clock for deer mice was trained on 3 tissues (tail, liver, and brain). Two human-Peromyscusclocks accurately measure age and relative age, respectively. We present CpGs and enriched pathways that relate to different conditions such as chronological age, high altitude, and monogamous behavior. Overall, this study provides a first step towards studying the epigenetic correlates of monogamous behavior and adaptation to high altitude inPeromyscus. The human-Peromyscusepigenetic clocks are expected to provide a significant boost to the attractiveness ofPeromyscusas a biological model.

     
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  2. Abstract

    Longevity plays a key role in the fitness of organisms, so understanding the processes that underlie variance in senescence has long been a focus of ecologists and evolutionary biologists. For decades, the performance and ultimate decline of mitochondria have been implicated in the demise of somatic tissue, but exactly why mitochondrial function declines as individual’s age has remained elusive. A possible source of decline that has been of intense debate is mutations to the mitochondrial DNA. There are two primary sources of such mutations: oxidative damage, which is widely discussed by ecologists interested in aging, and mitochondrial replication error, which is less familiar to most ecologists. The goal of this review is to introduce ecologists and evolutionary biologists to the concept of mitochondrial replication error and to review the current status of research on the relative importance of replication error in senescence. We conclude by detailing some of the gaps in our knowledge that currently make it difficult to deduce the relative importance of replication error in wild populations and encourage organismal biologists to consider this variable both when interpreting their results and as viable measure to include in their studies.

     
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  3. ABSTRACT

    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.

     
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  4. Abstract

    An important component of life history theory is understanding how natural variation arises in populations. Both endogenous and exogenous factors contribute to organism survival and reproduction, and therefore, it is important to understand how such factors are both beneficial and detrimental to population dynamics. One ecologically relevant factor that influences the life history of aquatic organisms is ultraviolet (UV) radiation. While the majority of research has focused on the potentially detrimental effects that UV radiation has on aquatic organisms, few studies have evaluated hormetic responses stimulated by radiation under select conditions. The goal of this study was to evaluate the impact of UV‐A/B irradiation on life history characteristics inTigriopus californicuscopepods. After exposing copepods to UV‐A/B irradiation (control, 1‐, and 3‐hr UV treatments at 0.5 W/m2), we measured the impact of exposure on fecundity, reproductive effort, and longevity. We found that UV irradiation increased the size of the first clutch among all reproducing females in both the 1‐ and 3‐hr experimental groups and decreased longevity among all females that mated in the 1‐hr treatment. UV irradiation had no effect on the number of clutches females produced. These findings indicate a potential benefit of UV irradiation on reproductive performance early in life, although the same exposure came at a cost to longevity.

     
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  5. Abstract

    Eukaryotes are the outcome of an ancient symbiosis and as such, eukaryotic cells fundamentally possess two genomes. As a consequence, gene products encoded by both nuclear and mitochondrial genomes must interact in an intimate and precise fashion to enable aerobic respiration in eukaryotes. This genomic architecture of eukaryotes is proposed to necessitate perpetual coevolution between the nuclear and mitochondrial genomes to maintain coadaptation, but the presence of two genomes also creates the opportunity for intracellular conflict. In the collection of papers that constitute this symposium volume, scientists working in diverse organismal systems spanning vast biological scales address emerging topics in integrative, comparative biology in light of mitonuclear interactions.

     
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  6. null (Ed.)
    Abstract Background Genes that belong to the same network are frequently co-expressed, but collectively, how the coordination of the whole transcriptome is perturbed during aging remains unclear. To explore this, we calculated the correlation of each gene in the transcriptome with every other, in the brain of young and older outbred deer mice (P. leucopus and P. maniculatus). Results In about 25 % of the genes, coordination was inversed during aging. Gene Ontology analysis in both species, for the genes that exhibited inverse transcriptomic coordination during aging pointed to alterations in the perception of smell, a known impairment occurring during aging. In P. leucopus, alterations in genes related to cholesterol metabolism were also identified. Among the genes that exhibited the most pronounced inversion in their coordination profiles during aging was THBS4, that encodes for thrombospondin-4, a protein that was recently identified as rejuvenation factor in mice. Relatively to its breadth, abolishment of coordination was more prominent in the long-living P. leucopus than in P. maniculatus but in the latter, the intensity of de-coordination was higher. Conclusions There sults suggest that aging is associated with more stringent retention of expression profiles for some genes and more abrupt changes in others, while more subtle but widespread changes in gene expression appear protective. Our findings shed light in the mode of the transcriptional changes occurring in the brain during aging and suggest that strategies aiming to broader but more modest changes in gene expression may be preferrable to correct aging-associated deregulation in gene expression. 
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  7. null (Ed.)
    Abstract Background Deregulation in lipid metabolism leads to the onset of hepatic steatosis while at subsequent stages of disease development, the induction of inflammation, marks the transition of steatosis to non-alcoholic steatohepatitis. While differential gene expression unveils individual genes that are deregulated at different stages of disease development, how the whole transcriptome is deregulated in steatosis remains unclear. Methods Using outbred deer mice fed with high fat as a model, we assessed the correlation of each transcript with every other transcript in the transcriptome. The onset of steatosis in the liver was also evaluated histologically. Results Our results indicate that transcriptional reprogramming directing immune cell engagement proceeds robustly, even in the absence of histologically detectable steatosis, following administration of high fat diet. In the liver transcriptomes of animals with steatosis, a preference for the engagement of regulators of T cell activation and myeloid leukocyte differentiation was also recorded as opposed to the steatosis-free livers at which non-specific lymphocytic activation was seen. As compared to controls, in the animals with steatosis, transcriptome was subjected to more widespread reorganization while in the animals without steatosis, reorganization was less extensive. Comparison of the steatosis and non-steatosis livers showed high retention of coordination suggesting that diet supersedes pathology in shaping the transcriptome’s profile. Conclusions This highly versatile strategy suggests that the molecular changes inducing inflammation proceed robustly even before any evidence of steatohepatitis is recorded, either histologically or by differential expression analysis. 
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