Hormetic Mechanisms of Anti-Aging and Rejuvenating Effects of Repeated Mild Heat Stress on Human Fibroblasts in Vitro

2004 ◽  
Vol 7 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Suresh I. S. Rattan
10.1379/475.1 ◽  
2004 ◽  
Vol 9 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Rasmus Beedholm ◽  
Brian F.C. Clark ◽  
Suresh I.S. Rattan

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.


2013 ◽  
Vol 305 (3) ◽  
pp. C323-C333 ◽  
Author(s):  
Tetsuo Yamaguchi ◽  
Maiko Omori ◽  
Nobuho Tanaka ◽  
Naoshi Fukui

Ingestion of sodium bicarbonate (NaHCO3) is known to enhance athletic performance, probably via increased extracellular buffering capacity. At present, little is known about the direct effects of NaHCO3 on myogenesis, especially in vitro. Here, we examined the effects of NaHCO3 and the combined effects of NaHCO3 and continuous mild heat stress (CMHS) at 39°C on the differentiation of human skeletal muscle myoblasts (HSMMs). Levels of myosin heavy chain (MyHC) type I mRNA increased with increasing NaHCO3 concentrations; in contrast, those of MyHC IIx decreased. The NaHCO3-induced fast-to-slow shift was additively enhanced by CMHS. Likewise, intracellular calcium levels and expression of three factors, nuclear factor of activated T cells c2 (NFATc2), NFATc4, and peroxisome-proliferator-activated receptor-γ coactivator-1α, were upregulated with increasing NaHCO3 concentrations; moreover, these effects of NaHCO3 were additively enhanced by CMHS. Overexpression experiments and small interfering RNA-mediated knockdown experiments confirmed that NFATc2 and NFATc4 were involved in MyHC I regulation. The present study provided evidence that NaHCO3 and CMHS distinctly and additively induced a fast-to-slow fiber type shift through changes in intracellular calcium levels and the modulation of calcium signaling.


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.


2012 ◽  
Vol 35 (8) ◽  
pp. 1371-1373 ◽  
Author(s):  
Tamaki Cho ◽  
Jun-ichi Nagao ◽  
Rieko Imayoshi ◽  
Jun Kodama ◽  
Takahiko Morotomi ◽  
...  

2011 ◽  
Vol 81 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Joel Deneau ◽  
Taufeeq Ahmed ◽  
Roger Blotsky ◽  
Krzysztof Bojanowski

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.


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