scholarly journals Slowing down aging from within: mechanistic aspects of anti-aging hormetic effects of mild heat stress on human cells.

2004 ◽  
Vol 51 (2) ◽  
pp. 481-492 ◽  
Author(s):  
Suresh I S Rattan ◽  
Regina Gonzalez-Dosal ◽  
Elise Rørge Nielsen ◽  
David Christian Kraft ◽  
Jens Weibel ◽  
...  

Since aging is primarily the result of a failure of maintenance and repair mechanisms, various approaches are being developed in order to stimulate these pathways and modulate the process of aging. One such approach, termed hormesis, involves challenging cells and organisms by mild stress that often results in anti-aging and life prolonging effects. In a series of experimental studies, we have reported that repeated mild heat stress (RMHS) has anti-aging hormetic effects on growth and various cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. These beneficial effects of repeated challenge include the maintenance of stress protein profile, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to other stresses, and enhanced levels of cellular antioxidant ability. In order to elucidate the molecular mechanisms of hormetic effects of RMHS, we are now undertaking studies on signal transduction pathways, energy production and utilisation kinetics, and the proteomic analysis of patterns of proteins synthesised and their posttranslational modifications in various types of human cells undergoing cellular aging in vitro. Human applications of hormesis include early intervention and modulation of the aging process to prevent or delay the onset of age-related conditions, such as sarcopenia, Alzheimer's disease, Parkinson's disease, cataracts and osteoporosis.

Dose-Response ◽  
2005 ◽  
Vol 3 (4) ◽  
pp. dose-response.0 ◽  
Author(s):  
Suresh I. S. Rattan

Aging is characterized by a stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. In a series of experimental studies we have shown that repetitive mild heat stress has anti-aging hormetic effects on growth and various other cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. These effects include the maintenance of stress protein profiles, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the proteasomal activities for the degradation of abnormal proteins, improved cellular resistance to ethanol, hydrogenperoxide and ultraviolet-B rays, and enhanced levels of various antioxidant enzymes. Anti-aging hormetic effects of mild heat shock appear to be facilitated by reducing protein damage and protein aggregation by activating internal antioxidant, repair and degradation processes.


2004 ◽  
Vol 2 (2) ◽  
pp. 154014204904643 ◽  
Author(s):  
Suresh I. S. Rattan ◽  
Yvonne E. G. Eskildsen-Helmond ◽  
Rasmus Beedholm

2021 ◽  
Author(s):  
Hayat Ali Alafari ◽  
Magda Abdelgawad

Abstract BackgroundWithin their natural habitat, plants are subjected to abiotic stresses that include heat stress. In the current study, the effect of 4h, 24h and 48h of heat stress on Tetraena propinqua ssp. migahidii seedling’s protein profile and proteomic analyses were investigated. ResultsTotal soluble protein SDS-PAGE profile showed 18-protein bands downregulated at 4h and 48h, however, 20-protein bands were upregulated at 24h of heat stress. A proteomic analysis showed that 81 and 59 targets are involved in gene and protein expression respectively. ConclusionsThe genes and proteins involved in transcription, translation, photosynthesis, transport and other unknown metabolic processes, were differentially expressed under treatments of heat stress. These findings provide insights into the molecular mechanisms related to heat stress, in addition to its influence on the physiological traits of T. propinqua seedlings. Heat stress mediated differential regulation genes indicate a role in development and stress response of T. propinqua. The candidate dual specificity genes identified in this study paves way for more molecular analysis of up- and down-regulation.


2021 ◽  
Vol 14 (10) ◽  
pp. 1040
Author(s):  
Dolors Puigoriol-Illamola ◽  
Júlia Companys-Alemany ◽  
Kris McGuire ◽  
Natalie Z. M. Homer ◽  
Rosana Leiva ◽  
...  

Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer’s disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The inhibition of this enzyme is linked with a reduction in GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could reverse the deleterious effects of CMS on cognition and behavioral abilities and to evaluate the molecular mechanisms that compromise healthy aging in SAMP8 mice. First, we confirmed the target engagement between RL-118 and 11β-HSD1. Additionally, we showed that DNA methylation, hydroxymethylation, and histone phosphorylation were decreased by CMS induction, and increased by RL-118 treatment. In addition, CMS exposure caused the accumulation of reactive oxygen species (ROS)-induced damage and increased pro-oxidant enzymes—as well as pro-inflammatory mediators—through the NF-κB pathway and astrogliosis markers, such as GFAP. Of note, these modifications were reversed by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signaling, autophagy was increased in the SAMP8 RL-118-treated mice. We also showed an increase in amyloidogenic processes and a decrease in synaptic plasticity and neuronal remodeling markers in mice under CMS, which were consequently modified by RL-118 treatment. In conclusion, 11β-HSD1 inhibition through RL-118 ameliorated the detrimental effects induced by CMS, including epigenetic and cognitive disturbances, indicating that GC-excess attenuation shows potential as a therapeutic strategy for age-related cognitive decline and AD.


2020 ◽  
Vol 202 (9) ◽  
Author(s):  
Duarte N. Guerreiro ◽  
Jialun Wu ◽  
Charlotte Dessaux ◽  
Ana H. Oliveira ◽  
Teresa Tiensuu ◽  
...  

ABSTRACT In Listeria monocytogenes, the full details of how stress signals are integrated into the σB regulatory pathway are not yet available. To help shed light on this question, we investigated a collection of transposon mutants that were predicted to have compromised activity of the alternative sigma factor B (σB). These mutants were tested for acid tolerance, a trait that is known to be under σB regulation, and they were found to display increased acid sensitivity, similar to a mutant lacking σB (ΔsigB). The transposon insertions were confirmed by whole-genome sequencing, but in each case, the strains were also found to carry a frameshift mutation in the sigB operon. The changes were predicted to result in premature stop codons, with negative consequences for σB activation, independently of the transposon location. Reduced σB activation in these mutants was confirmed. Growth measurements under conditions similar to those used during the construction of the transposon library revealed that the frameshifted sigB operon alleles conferred a growth advantage at higher temperatures, during late exponential phase. Mixed-culture experiments at 42°C demonstrated that the loss of σB activity allowed mutants to take over a population of parental bacteria. Together, our results suggest that mutations affecting σB activity can arise during laboratory culture because of the growth advantage conferred by these mutations under mild stress conditions. The data highlight the significant cost of stress protection in this foodborne pathogen and emphasize the need for whole-genome sequence analysis of newly constructed strains to confirm the expected genotype. IMPORTANCE In the present study, we investigated a collection of Listeria monocytogenes strains that all carried sigB operon mutations. The mutants all had reduced σB activity and were found to have a growth advantage under conditions of mild heat stress (42°C). In mixed cultures, these mutants outcompeted the wild type when mild heat stress was present but not at an optimal growth temperature. An analysis of 22,340 published L. monocytogenes genome sequences found a high rate of premature stop codons present in genes positively regulating σB activity. Together, these findings suggest that the occurrence of mutations that attenuate σB activity can be favored under conditions of mild stress, probably highlighting the burden on cellular resources that stems from deploying the general stress response.


2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Maria D. Pinazo-Durán ◽  
Francisco Gómez-Ulla ◽  
Luis Arias ◽  
Javier Araiz ◽  
Ricardo Casaroli-Marano ◽  
...  

Purpose. To review the proposed pathogenic mechanisms of age macular degeneration (AMD), as well as the role of antioxidants (AOX) and omega-3 fatty acids (ω-3) supplements in AMD prevention.Materials and Methods. Current knowledge on the cellular/molecular mechanisms of AMD and the epidemiologic/experimental studies on the effects of AOX andω-3 were addressed all together with the scientific evidence and the personal opinion of professionals involved in the Retina Group of the OFTARED (Spain).Results. High dietary intakes ofω-3 and macular pigments lutein/zeaxanthin are associated with lower risk of prevalence and incidence in AMD. The Age-Related Eye Disease study (AREDS) showed a beneficial effect of high doses of vitamins C, E, beta-carotene, and zinc/copper in reducing the rate of progression to advanced AMD in patients with intermediate AMD or with one-sided late AMD. The AREDS-2 study has shown that lutein and zeaxanthin may substitute beta-carotene because of its potential relationship with increased lung cancer incidence.Conclusion. Research has proved that elder people with poor diets, especially with low AOX andω-3 micronutrients intake and subsequently having low plasmatic levels, are more prone to developing AMD. Micronutrient supplementation enhances antioxidant defense and healthy eyes and might prevent/retard/modify AMD.


2019 ◽  
Vol 14 (9) ◽  
pp. 1934578X1987640
Author(s):  
Li-Juan Deng ◽  
Yu-He Lei ◽  
Tsz-Fung Chiu ◽  
Ming Qi ◽  
Hua Gan ◽  
...  

Paeoniflorin (PF) is an important pharmacological component of some Chinese traditional herbal formulas, such as Bai Shao, Chi Shao, and Dan Pi, which have been clinically used for centuries. Although many experimental studies have explored a wide range of pharmacological properties of PF, including anticancer, anti-inflammatory, antioxidant, immunoregulatory, and prevention of insulin resistance, there is no review to describe these reported effects systematically, especially the antitumor effect and the underlying mechanisms. In this review, we summarize the recent progress on the anticancer profiles both in vitro and in vivo of PF. Moreover, we highlight the integrated molecular mechanisms of PF and contemplate its future prospects as a potential anticancer drug.


2019 ◽  
Vol 39 (8) ◽  
pp. 1285-1299 ◽  
Author(s):  
Nadine K Ruehr ◽  
Rüdiger Grote ◽  
Stefan Mayr ◽  
Almut Arneth

Abstract Plant responses to drought and heat stress have been extensively studied, whereas post-stress recovery, which is fundamental to understanding stress resilience, has received much less attention. Here, we present a conceptual stress-recovery framework with respect to hydraulic and metabolic functioning in woody plants. We further synthesize results from controlled experimental studies following heat or drought events and highlight underlying mechanisms that drive post-stress recovery. We find that the pace of recovery differs among physiological processes. Leaf water potential and abscisic acid concentration typically recover within few days upon rewetting, while leaf gas exchange-related variables lag behind. Under increased drought severity as indicated by a loss in xylem hydraulic conductance, the time for stomatal conductance recovery increases markedly. Following heat stress release, a similar delay in leaf gas exchange recovery has been observed, but the reasons are most likely a slow reversal of photosynthetic impairment and other temperature-related leaf damages, which typically manifest at temperatures above 40 °C. Based thereon, we suggest that recovery of gas exchange is fast following mild stress, while recovery is slow and reliant on the efficiency of repair and regrowth when stress results in functional impairment and damage to critical plant processes. We further propose that increasing stress severity, particular after critical stress levels have been reached, increases the carbon cost involved in reestablishing functionality. This concept can guide future experimental research and provides a base for modeling post-stress recovery of carbon and water relations in trees.


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