scholarly journals The Naked Mole Rat: A Unique Example of Positive Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Frédéric Saldmann ◽  
Melanie Viltard ◽  
Christine Leroy ◽  
Gérard Friedlander
Keyword(s):  
Oxidative Stress ◽  
Successful Aging ◽  
Second Messengers ◽  
Mitochondrial Oxidative Stress ◽  
Stress Theory ◽  
Cellular Processes ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
In Captivity

The oxidative stress theory of aging, linking reactive oxygen species (ROS) to aging, has been accepted for more than 60 years, and numerous studies have associated ROS with various age-related diseases. A more precise version of the theory specifies that mitochondrial oxidative stress is a direct cause of aging. The naked mole rat, a unique animal with exceptional longevity (32 years in captivity), appears to be an ideal model to study successful aging and the role of ROS in this process. Several studies in the naked mole rat have shown that these animals exhibit a remarkable resistance to oxidative stress. At low concentrations, ROS serve as second messengers, and these important intracellular signalling functions are crucial for the regulation of cellular processes. In this review, we examine the literature on ROS and their functions as signal transducers. We focus specifically on the longest-lived rodent, the naked mole rat, which is a perfect example of the paradox of living an exceptionally long life with slow aging despite high levels of oxidative damage from a young age.

Vascular aging in the longest-living rodent, the naked mole rat

2007 ◽  
Vol 293 (2) ◽  
pp. H919-H927 ◽  
Author(s):  
Anna Csiszar ◽  
Nazar Labinskyy ◽  
Zsuzsanna Orosz ◽  
Zhao Xiangmin ◽  
Rochelle Buffenstein ◽  
...  
Keyword(s):  
Cell Death ◽  
Vascular Function ◽  
Successful Aging ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
No Donor ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
Age Range

The naked mole rat (NMR; Heterocephalus glaber) is the longest-living rodent known [maximum lifespan potential (MLSP): >28 yr] and is a unique model of successful aging showing attenuated declines in most physiological function. This study addresses age-related changes in endothelial function and production of reactive oxygen species in NMR arteries and vessels of shorter-living Fischer 344 rats (MLSP: ∼3 yr). Rats exhibit a significant age-dependent decline in acetylcholine-induced responses in carotid arteries over a 2-yr age range. In contrast, over a 10-yr age range nitric oxide (NO)-mediated relaxation responses to acetylcholine and to the NO donor S-nitrosopencillamine (SNAP) were unaltered in NMRs. Cellular superoxide anion (O2•−) and H2O2 production significantly increased with age in rat arteries, whereas they did not change substantially with age in NMR vessels. Indicators of apoptotic cell death (DNA fragmentation rate, caspase 3/7 activity) were significantly enhanced (∼250–300%) in arteries of 2-yr-old rats. In contrast, vessels from 12-yr-old NMRs exhibited only a ∼50% increase in apoptotic cell death. In the hearts of NMRs (2 to 26 yr old), expression of endothelial NO synthase, antioxidant enzymes (Cu,Zn-SOD, Mn-SOD, catalase, and glutathione peroxidase), the NAD(P)H oxidase subunit gp91 phox, and mitochondrial proteins (COX-IV, ATP synthase, and porin, an indicator of mitochondrial mass) did not change significantly with age. Thus long-living NMRs can maintain a youthful vascular function and cellular oxidant-antioxidant phenotype relatively longer and are better protected against aging-induced oxidative stress than shorter-living rats.

scholarly journals Hematologic adaptation to the subterranean environment by the naked mole-rat, Heterocephalus glaber (Ctenohystrica: Heterocephalidae)

2020 ◽  
Vol 101 (4) ◽  
pp. 1000-1009
Author(s):  
Susanne Holtze ◽  
Rosie Koch ◽  
Thomas Bernd Hildebrandt ◽  
Alemayehu Lemma ◽  
Karol Szafranski ◽  
...  
Keyword(s):  
Blood Chemistry ◽  
Subterranean Rodents ◽  
Atmospheric Conditions ◽  
Heterocephalus Glaber ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
In Captivity ◽  
Surface Dwelling ◽  
Oxygen Carrying Capacity ◽  
Subterranean Environment

Abstract One method burrowing animals are hypothesized to use in adapting to the presumed hypoxic subterranean environment is increasing the oxygen-carrying capacity of blood. A number of recent studies have examined hematologic parameters in laboratory-reared naked mole-rats, but not in animals living under natural atmospheric conditions. To our knowledge, blood chemistry parameters have never been systematically assessed in a fossorial mammal. In this study we examined the blood of wild naked mole-rats in Kenya and Ethiopia to determine whether their blood chemistry differs significantly from naked mole-rats born and living in captivity. We also compared our results to published values for hystricomorphs, other subterranean rodents, and surface-dwelling rodents of similar size.

scholarly journals Intracellular cyclic AMP levels modulate differential adaptive responses on epimastigotes and cell culture trypomastigotes of Trypanosoma cruzi

2019 ◽  
Author(s):  
Tamara Sternlieb ◽  
Alejandra C. Schoijet ◽  
Guillermo D. Alonso
Keyword(s):  
Oxidative Stress ◽  
Trypanosoma Cruzi ◽  
Second Messengers ◽  
Redox Status ◽  
Adaptive Responses ◽  
Cellular Processes ◽  
The Many ◽  
Hemoglobin Degradation ◽  
Intracellular Second Messengers

ABSTRACTAmong the many environmental challenges the parasite Trypanosoma cruzi has to overcome to complete its life cycle through different hosts, oxidative stress plays a central role. Different stages of this parasite encounter distinct sources of oxidative stress, such as the oxidative burst of the immune system, or the Heme released from hemoglobin degradation in the triatomine’s midgut. Also, the redox status of the surroundings functions as a signal to the parasite, triggering processes coupled to differentiation or proliferation. Intracellular second messengers, like cAMP, are responsible for the transduction of environmental queues and initiating cellular processes accordingly. In trypanosomatids cAMP is involved in a variety of processes, including proliferation, differentiation, osmoregulation and quorum sensing. Trypanosomatid phosphodiesterases (PDE) show atypical pharmacological properties and some have been involved in key processes for the survival of the parasites, which validates them as attractive therapeutic targets. Our work here shows that cAMP modulates different processes according to parasite stage. Epimastigotes become more resistant to oxidative stress when pre-treated with cAMP analogs, while trypomastigotes do not alter their response to oxidative stress under the same treatment. However, cAMP analogs do increase trypomastigotes infectivity in vitro. Also, we show that TcrPDEA1, a functionally enigmatic phosphodiesterase with very high Km, is involved in the epimastigotes response to oxidative stress.

scholarly journals How the naked mole-rat resists senescence: a constraints-based theory

2021 ◽  
Author(s):  
Felipe A. Veloso
Keyword(s):  
House Mouse ◽  
House Mice ◽  
Nucleosome Core Particle ◽  
Chromatin Dynamics ◽  
Nucleosome Core ◽  
Differentiated Cells ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
Histone Modifying Enzymes

Here, I present a theory describing how the stabilization of constraints imposed on chromatin dynamics by the naked mole-rat's histone H1.0 protein—which in terminally differentiated cells constrains the accessibility of the nucleosome core particle for histone-modifying enzymes and chromatin remodeling factors—explains its resistance to both senescence and cancer. Further, this theory predicts that a mutant house mouse displaying such stabilization will be similarly resistant to both senescence and cancer. A proof-of-concept computational analysis is presented and two predictions for the direct testing of the theory are provided. These experiments comprise, as test subjects, mutant naked mole-rats synthesizing a house mouse (Mus musculus)-like histone H1.0, and mutant house mice synthesizing a naked mole-rat-like histone H1.0. The predictions are that the constraints on chromatin dynamics embodied by the respective mutant histone H1.0 proteins will negate the otherwise significant resistance to both senescence and cancer of the naked mole-rats and, conversely, confer such resistance to the house mice. A verification of these predictions will imply that constraints on chromatin dynamics embodied by naked mole-rat-like histone H1.0 proteins may confer significant resistance to both senescence and age-related cancer to otherwise senescence-prone and/or cancer-susceptible multicellular species, including humans.

scholarly journals Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders

Antioxidants ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 102 ◽  
Author(s):  
Giuseppina Barrera ◽  
Stefania Pizzimenti ◽  
Martina Daga ◽  
Chiara Dianzani ◽  
Alessia Arcaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Structural Damage ◽  
Membrane Lipids ◽  
Biological Fluids ◽  
Second Messengers ◽  
Biological Macromolecules ◽  
Age Related ◽  
Distinct Cell ◽  
Reactive Aldehydes

Among the various mechanisms involved in aging, it was proposed long ago that a prominent role is played by oxidative stress. A major way by which the latter can provoke structural damage to biological macromolecules, such as DNA, lipids, and proteins, is by fueling the peroxidation of membrane lipids, leading to the production of several reactive aldehydes. Lipid peroxidation-derived aldehydes can not only modify biological macromolecules, by forming covalent electrophilic addition products with them, but also act as second messengers of oxidative stress, having relatively extended lifespans. Their effects might be further enhanced with aging, as their concentrations in cells and biological fluids increase with age. Since the involvement and the role of lipid peroxidation-derived aldehydes, particularly of 4-hydroxynonenal (HNE), in neurodegenerations, inflammation, and cancer, has been discussed in several excellent recent reviews, in the present one we focus on the involvement of reactive aldehydes in other age-related disorders: osteopenia, sarcopenia, immunosenescence and myelodysplastic syndromes. In these aging-related disorders, characterized by increases of oxidative stress, both HNE and malondialdehyde (MDA) play important pathogenic roles. These aldehydes, and HNE in particular, can form adducts with circulating or cellular proteins of critical functional importance, such as the proteins involved in apoptosis in muscle cells, thus leading to their functional decay and acceleration of their molecular turnover and functionality. We suggest that a major fraction of the toxic effects observed in age-related disorders could depend on the formation of aldehyde-protein adducts. New redox proteomic approaches, pinpointing the modifications of distinct cell proteins by the aldehydes generated in the course of oxidative stress, should be extended to these age-associated disorders, to pave the way to targeted therapeutic strategies, aiming to alleviate the burden of morbidity and mortality associated with these disturbances.

scholarly journals Telomeres and Longevity: A Cause or an Effect?

2019 ◽  
Vol 20 (13) ◽  
pp. 3233 ◽  
Author(s):  
Huda Adwan Shekhidem ◽  
Lital Sharvit ◽  
Eva Leman ◽  
Irena Manov ◽  
Asael Roichman ◽  
...  
Keyword(s):  
Telomere Length ◽  
Ongoing Debate ◽  
Telomere Attrition ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
Extreme Longevity ◽  
Linear Chromosomes ◽  
Biological State

Telomere dynamics have been found to be better predictors of survival and mortality than chronological age. Telomeres, the caps that protect the end of linear chromosomes, are known to shorten with age, inducing cell senescence and aging. Furthermore, differences in age-related telomere attrition were established between short-lived and long-lived organisms. However, whether telomere length is a “biological thermometer” that reflects the biological state at a certain point in life or a biomarker that can influence biological conditions, delay senescence and promote longevity is still an ongoing debate. We cross-sectionally tested telomere length in different tissues of two long-lived (naked mole-rat and Spalax) and two short-lived (rat and mice) species to tease out this enigma. While blood telomere length of the naked mole-rat (NMR) did not shorten with age but rather showed a mild elongation, telomere length in three tissues tested in the Spalax declined with age, just like in short-lived rodents. These findings in the NMR, suggest an age buffering mechanism, while in Spalax tissues the shortening of the telomeres are in spite of its extreme longevity traits. Therefore, using long-lived species as models for understanding the role of telomeres in longevity is of great importance since they may encompass mechanisms that postpone aging.

Abstract 316: Enhanced Cardiac Proteasome Function in the Naked Mole-rat, the Longest-lived Rodent

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
David A Kramer ◽  
Kelly M Grimes ◽  
Rochelle Buffenstein
Keyword(s):  
Qualitative Difference ◽  
Physiological Role ◽  
Ubiquitin Proteasome System ◽  
Proteasome Activity ◽  
Mouse Heart ◽  
Atp Levels ◽  
Age Related ◽  
Mole Rat ◽  
Naked Mole Rat ◽  
Heart Disorders

The ubiquitin-proteasome system (UPS) is responsible for the recycling of misfolded proteins. Dysfunction of the UPS has been implicated in the pathophysiology of multiple heart disorders, including heart failure and reperfusion injury, but the basic science of cardiac UPS function remains unclear. An attractive mode of inquiry into the cardiac proteasome is the long-lived naked mole rat (NMR), which maintains intact cardiac reserve and diastolic function exceptionally late into its lifespan; equivalent to a 90 year old human with a 30 year old’s heart. In this study, we investigated whether the long-lived and healthful NMR had upregulated aspects of UPS function in comparison to the short-lived well-characterized mouse. NMR hearts have more than twofold (p<0.001) greater proteasome-mediated chymotrypsin-like activity than mouse hearts. NMR hearts also have significantly greater levels of proteasome subunits than mice, including α7 and Rpt5, suggesting that the greater numbers of proteasomes could contribute to the high chymotrypsin-like activity, alternatively, the naked mole-rat heart may also have more immunoproteasomes which are more efficient. The UPS is energy-dependent, with its activity significantly influenced by available ATP. Interestingly, basal ATP levels were 40 to 50 fold higher in NMR hearts than in those of mice. This is consistent with the much larger pools of mitochondria observed in the NMR heart than in the mouse heart. Considering that both high and low ATP levels are associated with a decline in proteasome activity, we next asked whether the remarkably high basal ATP levels of the NMR heart caused a qualitative difference in UPS function between NMRs and mice. Levels of ubiquitinated protein were significantly lower in the NMR heart than in the mouse heart, suggesting that the NMR cardiac UPS system is more effective at destroying ubiquitin-tagged damaged proteins than that of the mouse, and that the NMR heart’s elevated ATP levels may play a physiological role in maintaining this enhanced UPS functionality. Overall these data suggest a high basal level of proteasome activity in the NMR heart that may be of paramount importance in this animal’s ability to withstand and/or prevent age-related cardiovascular functional declines.

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