Hormesis can and Does Work in Humans

Rattan, Suresh I. S.; Demirovic, Dino

doi:10.2203/dose-response.09-041.rattan

Cited by 52 publications

(56 citation statements)

References 26 publications

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“…As discussed above, cells and tissues can react against exercise-induced free radicals by molecular pathways involving triggering NFkB, which in turn stimulates protein kinases that can activate other protein mitogen-activated kinases (MAPK), or the zinc-containing nuclear respiratory transcription factor-2 (Nrf-2) (George et al 2008) or even activating the forkhead box proteins (FOXO) (Rattan and Ali 2007;Rattan and Demirovic 2010;Yin et al 2010). In the absence of insulin and insulin-growth factor-1 (IGF-1), FOXO can trigger the kinase protein pathway, akt, which in turn activates the adenosine monophosphate activated protein kinase (AMP-kinase or AMPK) resulting in cell proliferation, survival, suppressing of tumors, and longevity (Greer and Brunet 2005;Greer et al 2007).…”

Section: Tac In Aging and Detraining: Is The Lack Of Exercise The Orimentioning

confidence: 99%

“…Chronic AMPK activation due to exercise improves muscle oxidative metabolism, increasing myogenic responses (Llubicic et al 2011). The FOXO3A gene which encodes information for the synthesis of FOXO proteins has been considered a longevity gene in very different cell types (Anselmi et al 2009;Rattan and Demirovic 2010). It should be noted that on contrast to other tissues and organs, in skeletal muscles akt is a survival pathway and FOXO proteins mediate myostatin-induced sarcopenia (Greer and Brunet 2005;Favier et al 2008).…”

Section: Tac In Aging and Detraining: Is The Lack Of Exercise The Orimentioning

confidence: 99%

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Exercise modulation of total antioxidant capacity (TAC): towards a molecular signature of healthy aging

Ferrari

2011

Frontiers in Life Science

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The objective of this article was to review the biochemical basis of the total antioxidant capacity (TAC) test and its applications to exercise science and promotion of healthy aging. Measurement of TAC allows evaluation of the antioxidant content of muscle, heart and other exercise-target organs. Acute non-regular physical exercise and body exposition to higher altitude have been associated with a considerable decrease of blood TAC. However, regular practice of physical activity and exercise is associated with improved antioxidant response increasing TAC levels. TAC methodologies did not address lipophylic antioxidants and have some other limitations. However, TAC is useful as a complementary test for the evaluation of antiperoxidation assays and blood, erythrocyte and cytosolic antioxidant enzyme assays (glutathion reductase, glutathion peroxidase, superoxide dismutase and catalase). Exercise induces both molecular antioxidant and hormetic responses which have been suggested to be linked with a healthy aging.

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Section: Tac In Aging and Detraining: Is The Lack Of Exercise The Orimentioning

confidence: 99%

Section: Tac In Aging and Detraining: Is The Lack Of Exercise The Orimentioning

confidence: 99%

Exercise modulation of total antioxidant capacity (TAC): towards a molecular signature of healthy aging

Ferrari

2011

Frontiers in Life Science

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“…The pathological hallmark of tauopathies such as AD is neuronal inclusions of tau protein. If all forms of oxidative stress induce the accumulation of tau and tau dysfunction, then the beneficial effects of exercise on AD cannot simply be explained by the causal role of oxidative stress, considering the fact that substantial amounts of ROS are generated during exercise (Rattan & Demirovic, 2010). Even though H 2 O 2 accumulates with aging, it may not be the cause of aging (Cocheme et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is perhaps not only the oxidative stress but also the resistance mechanisms against oxidative stress that may determine the rate of aging (Perez et al, 2009). Such adaptive stress responses might underlie hormesis, a phenomenon in which a compound that, at higher levels, produces deleterious effects, but at lower levels, produces beneficial effects (Mattson, 2008;Rattan & Demirovic, 2010). If low levels of ROS could delay aging processes under certain conditions, we surmised that there is also a hormetic condition that exists during oxidative stress that prevents protein misfolding and associated dysfunctions.…”

Section: Introductionmentioning

confidence: 99%

Adaptive responses to alloxan‐induced mild oxidative stress ameliorate certain tauopathy phenotypes

et al. 2011

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SummaryOxidative stress is considered to promote aging and age-related disorders such as tauopathy. Although recent reports suggest that oxidative stress under certain conditions possesses anti-aging properties, no such conditions have been reported to ameliorate protein-misfolding diseases. Here, we used neuronal and murine models that overexpress human tau to demonstrate that mild oxidative stress generated by alloxan suppresses several phenotypes of tauopathy. Alloxan treatment reduced HSP90 levels and promoted proteasomal degradation of tau, c-Jun N-amino terminal kinase, and histone deacetylase (HDAC) 6. Moreover, reduced soluble tau (phosphorylated tau) levels suppressed the formation of insoluble tau in tau transgenic mice, while reduced HDAC6 levels contributed to microtubule stability by increasing tubulin acetylation. Age-dependent decreases in HDAC2 and phospho-tau levels correlated with spatial memory enhancement in alloxan-injected tau mice. These results suggest that mild oxidative stress, through adaptive stress responses, operates counteractively against some of the tauopathy phenotypes.

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“…In this context, the term "stress" is defined as a signal generated by any physical, chemical or biological factor (stressor), which in a living system initiates a series of events in order to counteract, adapt and survive. There are seven main pathways of SR intrinsic to cells: heat shock response (HSR), unfolded protein response (UPR), autophagy, antioxidant response, inflammatory response, DNA repair response and sirtuin response (Rattan and Demirovic, 2010a;2010b). Not all pathways of SR respond to every stressor, and although there may be some overlap, generally SR pathways are quite specific.…”

Section: S I S Rattan and Othersmentioning

confidence: 99%

Hormesis-Based Anti-Aging Products: A Case Study of a Novel Cosmetic

et al. 2012

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ᮀ Application of hormesis in aging research and interventions is becoming increasingly attractive and successful. The reason for this is the realization that mild stress-induced activation of one or more stress response (SR) pathways, and its consequent stimulation of repair mechanisms, is effective in reducing the age-related accumulation of molecular damage. For example, repeated heat stress-induced synthesis of heat shock proteins has been shown to have a variety of anti-aging effects on growth and other cellular and biochemical characteristics of normal human skin fibroblasts, keratinocytes and endothelial cells undergoing aging in vitro. Therefore, searching for potential hormetins -conditions and compounds eliciting SR-mediated hormesis -is drawing attention of not only the researchers but also the industry involved in developing healthcare products, including nutriceuticals, functional foods and cosmeceuticals. Here we present the example of a skin care cosmetic as one of the first successful product developments incorporating the ideas of hormesis. This was based on the studies to analyse the molecular effects of active ingredients extracted from the roots of the Chinese herb Sanchi (Panax notoginseng) on gene expression at the level of mRNAs and proteins in human skin cells. The results showed that the ginsenosides extracted from Sanchi induced the transcription of stress genes and increased the synthesis of stress proteins, especially the heat shock protein HSP1A1 or Hsp70, in normal human keratinocytes and dermal fibroblasts. Furthermore, this extract also has significant positive effects against facial wrinkles and other symptoms of facial skin aging as tested clinically, which may be due to its hormetic mode of action by stressinduced synthesis of chaperones involved in protein repair and removal of abnormal proteins. Acceptance of such a hormesis-based product by the wider public could be instrumental in the social recognition of the concept of hormesis as the beneficial effects of mild stress of choice, and will encourage the development of novel health care products with physical, nutritional and mental hormetins.

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Hormesis can and Does Work in Humans

Cited by 52 publications

References 26 publications

Exercise modulation of total antioxidant capacity (TAC): towards a molecular signature of healthy aging

Exercise modulation of total antioxidant capacity (TAC): towards a molecular signature of healthy aging

Adaptive responses to alloxan‐induced mild oxidative stress ameliorate certain tauopathy phenotypes

Hormesis-Based Anti-Aging Products: A Case Study of a Novel Cosmetic

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