A Case for Caution: An Evaluation of Calabrese and Baldwin\u27s Studies of Chemical Hormesis

Suggesting a need for more research, Mr. Elliott argues that it is too soon for risk-assessment policy to account for recent challenges to a toxicological linear dose-response assumption

Exercise epigenetics and the foetal origins of disease

Exercise epigenetics is a nascent area of research with vast health implications (e.g., from the treatment of obesity-related diseases to beneficially decoupling epigenetic and chronological age). Evidence is accumulating [1] that exercise can acutely modify the epigenome (e.g., via DNA methylation) for short-term regulatory purposes (e.g., mRNA expression). More speculatively perhaps, maternal exercise during the pre and post–partum period could cause epigenetic changes in offspring. It is generally believed that there are benefits of regular moderate exercise during pregnancy [2]. The phenotypic benefits of maternal exercise notwithstanding, exercise can be viewed as a type of organismal stressor [1]. There are a myriad of ways in which environmental perturbations can affect foetal development. For example gestational stress could alter the epigenome and subsequent physical development. We suggest that maternal exercise -- like most gestational stressors -- will have a dose-response relationship on an offspring’s epigenome (i.e., negative effects at high doses), akin to the phenomenon of hormesis. Interestingly there is no research investigating the epigenetic effects of maternal exercise in humans. This editorial is a call for research on the subject

Hormesis and Its Place in Nonmonotonic Dose–Response Relationships: Some Scientific Reality Checks

OBJECTIVE: This analysis is a critical assessment of current hormesis literature. I discuss definitions, characterization, generalizability, mechanisms, absence of empirical data specific for hormesis hypothesis testing, and arguments that hormesis be the “default assumption” in risk assessment. DATA SOURCES: Hormesis, a biological phenomenon typically described as low-dose stimulation from substances producing higher-dose inhibition, has recently garnered interest in several quarters. The principal sources of published materials for this analysis are the writings of certain proponents of hormesis. Surprisingly few systematic critiques of current hormesis literature exist. Limits to the phenomenon’s appropriate role in risk assessment and health policy have been published. DATA SYNTHESIS: Serious gaps in scientific understanding remain: a stable definition; generalizability, especially for humans; a clear mechanistic basis; limitations in the presence of multiple toxic end points, target organs, and mechanisms. Absence of both arms-length, consensus-driven, scientific evaluations and empirical data from studies specifically designed for hormesis testing have limited its acceptance. CONCLUSIONS: Definition, characterization, occurrence, and mechanistic rationale for hormesis will remain speculative, absent rigorous studies done specifically for hormesis testing. Any role for hormesis in current risk assessment and regulatory policies for toxics remains to be determined

Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint

The Degree of Genetic Overlap between Dietary Restriction and Hormesis

The ability of an organism to respond to environmental stress is an important indicator of how it will age. Two life-extension protocols, dietary restriction (DR) and hormesis, are thought to extend life by placing stress on an organism which then up-regulates its own stress- response systems. Because many researchers believe that DR is a form of hormesis, it is important to determine whether the genetic pathways behind these two protocols overlap. To answer this question, this study tested 14 candidate genes for requirement in either DR or hormesis. While there was little genetic overlap between DR and hormesis, two genes in the insulin- signaling pathway, daf-16 and daf-18, were partially required for both protocols. Moreover, the mitochondrial ribosomal protein B0261.4 was required for heat-induced hormesis, although the components of the electron transport chain tested were not required. The results of this study indicate two mostly-separate stress- response pathways and suggest that hormesis and DR might not function through the same mechanism. The most interesting result of this thesis is the possible requirement of mitochondrial ribosomal function in heat-induced hormesis. Further investigation into the role of mitochondrial ribosomal genes should be undertaken to determine the extent of requirement of mitochondrial protein translation in heat-induced hormesis

Hormesis: Path and Progression to Significance

This paper tells the story of how hormesis became recognized as a fundamental concept in biology, affecting toxicology, microbiology, medicine, public health, agriculture, and all areas related to enhancing biological performance. This paper assesses how hormesis enhances resilience to normal aging and protects against a broad spectrum of neurodegenerative, cardiovascular, and other diseases, as well as trauma and other threats to health and well-being. This paper also explains the application of hormesis to several neurodegenerative diseases such as Parkinson’s and Huntington’s disease, macrophage polarization and its systematic adaptive protections, and the role of hormesis in enhancing stem cell functioning and medical application

Effects of low-level deuterium enrichment on bacterial growth

Using very precise (up to 0.05%) measurements of the growth parameters for bacteria E. coli grown on minimal media, we aimed to determine the lowest deuterium concentration at which the adverse effects that are prominent at higher enrichments start to become noticeable. Such a threshold was found at 0.5% D, a surprisingly high value, while the ultralow deuterium concentrations (up to 0.25% D) showed signs of the opposite trend. Bacterial adaptation for 400 generations in isotopically different environment confirmed preference for ultralow (up to 0.25% D) enrichment. This effect appears to be similar to those described in sporadic but multiple earlier reports. Possible explanations include hormesis and isotopic resonance phenomena, with the latter explanation being favored.Comment: Accepted to PLoS One. Press embargo applie