Enhancing the human health and lifespan: a targeted strategy emphasizing statins.

There has been substantial research interest in finding activities/agents that slow the onset and reduce the severity of numerous age-related diseases/conditions. This assessment indicates that the most studied agent intended to promote health in human population investigations for a broad spectrum of diseases are the statins, with large-scale epidemiological studies addressing numerous health endpoints. The key findings are that statin treatment consistently reduces the occurrence and attenuates the course of numerous non-communicable and contagious pathologies and numerous types of cancer with high mortality rates by about 20-50%.

The Gofman-Tamplin Cancer Risk Controversy and Its Impact on the Creation of BEIR I and the Acceptance of LNT.

 The major public dispute between John Gofman and his colleague Arthur Tamplin and the United States (US) Atomic Energy Commission (AEC) at the end of the 1960s and during the early 1970s significantly impacted the course of cancer risk assessment in the US and worldwide. The challenging and provocative testimony of Gofman to the US Senate in early 1970 lead to the formation of the US National Academy of Sciences (NAS) Biological Effects of Ionizing Radiation (BEIR) I Committee in order to evaluate the accuracy of claims by Gofman and Tamplin that emissions from nuclear power plants would significantly increase the occurrence of genetic defects and cancers. BEIR I recommended the adoption of the linear non-threshold (LNT) dose response model for the assessment of cancer risks from radiation exposures.

Hormesis is an evolutionary expectation: implications for aging.

This article argues that evolution and the concept of hormesis are biologically inseparable. It proposes that evolutionary processes led to the selection of inducible adaptive hormetic strategies that are necessary for wellbeing and survival. Hormesis has been demonstrated in essentially all organisms in which it has been studied from bacteria to humans, showing its highly conserved features.

Enhancing health span: muscle stem cells and hormesis.

Sarcopenia is a significant public health and medical concern confronting the elderly. Considerable research is being directed to identify ways in which the onset and severity of sarcopenia may be delayed/minimized. This paper provides a detailed identification and assessment of hormetic dose responses in animal model muscle stem cells, with particular emphasis on cell proliferation, differentiation, and enhancing resilience to inflammatory stresses and how this information may be useful in preventing sarcopenia.

Curcumin, Hormesis and the Nervous System.

Curcumin is a polyphenol compound extracted from the rhizome of (family ) commonly used as a spice to color and flavor food. Several preclinical studies have suggested beneficial roles for curcumin as an adjuvant therapy in free radical-based diseases, mainly neurodegenerative disorders. Indeed, curcumin belongs to the family of hormetins and the enhancement of the cell stress response, mainly the heme oxygenase-1 system, is actually considered the common denominator for this dual response.

Two decades (1998-2018) of research Progress on Hormesis: advancing biological understanding and enabling novel applications.

This commentary briefly summarizes the extraordinary resurgence of hormesis within the biological, biomedical, toxicological and risk assessment domains over the past two decades. It places this resurgence within the context of challenging the scientific validity of the threshold and linear dose responses. It argues that conducting research on mechanisms that actuate and regulate the stimulatory response features of hormesis will provide the knowledge needed to develop potentially transformational applications aimed at protecting and enhancing biological resiliency as well as treating/curing a multitude of diverse medical conditions.

Muller's nobel prize research and peer review.

Background: This paper assesses possible reasons why Hermann J. Muller avoided peer-review of data that became the basis of his Nobel Prize award for producing gene mutations in male Drosophila by X-rays.

Methods: Extensive correspondence between Muller and close associates and other materials were obtained from preserved papers to compliment extensive publications by and about Muller in the open literature.

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 applications.

Was Muller's 1946 Nobel Prize research for radiation-induced gene mutations peer-reviewed?

This historical analysis indicates that it is highly unlikely that the Nobel Prize winning research of Hermann J. Muller was peer-reviewed. The published paper of Muller lacked a research methods section, cited no references, and failed to acknowledge and discuss the work of Gager and Blakeslee (PNAS 13:75-79, 1927) that claimed to have induced gene mutation via ionizing radiation six months prior to Muller's non-data Science paper (Muller, Science 66(1699):84-87, 1927a).

Nanoparticle Exposure and Hormetic Dose-Responses: An Update.

The concept of hormesis, as an adaptive response of biological systems to moderate environmental challenges, has raised considerable nano-toxicological interests in view of the rapid pace of production and application of even more innovative nanomaterials and the expected increasing likelihood of environmental and human exposure to low-dose concentrations. Therefore, the aim of this review is to provide an update of the current knowledge concerning the biphasic dose-responses induced by nanoparticle exposure. The evidence presented confirmed and extended our previous findings, showing that hormesis is a generalized adaptive response which may be further generalized to nanoscale xenobiotic challenges.

Post-conditioning hormesis creates a "subtraction to background" disease process: biological, aging, and environmental risk assessment implications.

The interaction of background disease processes with environmental induced diseases has long been an issue of considerable interest and debate with respect to its impact on risk assessment. Whether and to what extent these processes should be considered independent or additive to background has been the principal focus of debate. The concept of hormesis, a biphasic dose response characterized by a low dose stimulation and a high dose inhibition, as framed within the context of post-conditioning, reveal the occurrence of a third type of "background" possibility, that of "subtraction to background".

A glance into how the cold war and governmental loyalty investigations came to affect a leading U.S. radiation geneticist: Lewis J. Stadler's nightmare.

This paper describes an episode in the life of the prominent plant radiation geneticist, Lewis J. Stadler (1897-1954) during which he became a target of the Federal Bureau of Investigation (FBI) concerning loyalty to the United States due to possible associations with the communist party. The research is based on considerable private correspondence of Dr.

The Emergence of the Dose-Response Concept in Biology and Medicine.

A historical assessment of the origin of the dose-response in modern toxicology and its integration as a central concept in biology and medicine is presented. This article provides an overview of how the threshold, linear and biphasic (i.e.

Pre- and post-conditioning hormesis in elderly mice, rats, and humans: its loss and restoration.

This paper assessed differences and similarities in the capacity for preconditioning (PC) and post-conditioning (PostC) to prevent ischemic reperfusion (IR) damage to the heart in the old/elderly as compared to young adult mice, rats, and humans. While PC reliably reduces myocardial ischemia-induced heart damage by about 30-60 % in young adult (2-3 months old) mice and rats, such protection begins to diminish in middle age (1 year old) and is fully lost in the old and elderly (≥18 months). Common rearing practices (i.

What is hormesis and its relevance to healthy aging and longevity?

This paper provides a broad overview of hormesis, a specific type of biphasic dose response, its historical and scientific foundations as well as its biomedical applications, especially with respect to aging. Hormesis is a fundamental component of adaptability, neutralizing many endogenous and environmental challenges by toxic agents, thereby enhancing survival. Hormesis is highly conserved, broadly generalizable, and pleiotrophic, being independent of biological model, endpoint measured, inducing agent, level of biological organization and mechanism.

Origin of the linearity no threshold (LNT) dose-response concept.

This paper identifies the origin of the linearity at low-dose concept [i.e., linear no threshold (LNT)] for ionizing radiation-induced mutation.

Hormetic mechanisms.

This article provides the first extensive documentation of mechanisms of hormetic dose/concentration responses. The mechanisms selected were principally those mediated via receptor and/or cell signaling pathways. Mechanisms are reported for greater than 100 agents affecting nearly 400 dose/concentration responses from a wide range of chemical classes, affecting a broad range of cell types and endpoints.

X-Ray treatment of carbuncles and furuncles (boils): a historical assessment.

The goal of this article was to assess the historical role of radiotherapy in the treatment of selected inflammatory diseases. The specific research involved a literature-based assessment of the use of x-rays during the first half of the 20th century for the treatment of furuncles and carbuncles, the potentially serious staphylococcus infections. X-Rays were reported to be effective as a treatment at relatively low dose, about 10-20% of the skin erythema dose, which often quickly and profoundly reduce pain and accelerate the resolution/healing of the furuncles and carbuncles.

Low doses of radiation can enhance insect lifespans.

This paper assesses the capacity of ionizing radiation to extend the lifespans of experimental insect models based on the peer-reviewed literature. Ionizing radiation biphasically affects the lifespans of adult males and females for a broad range of insect models with high doses reducing lifespan whereas lower doses can enhance lifespan, typically in the 20-60 % range. The average adult insect lifespan can be increased when ionizing radiation exposure is administered during early developmental stages or during the adult stage.

Historical foundations of wound healing and its potential for acceleration: dose-response considerations.

This paper provides a detailed historical assessment of the origin and developmental progress of the concept of wound healing and its attempted acceleration from its start in the beginning of the 20th century to approximately 1960. Emphasis is placed on the development of cell culture in the assessment of wound healing and in attempts to validate experimental findings via clinical research. Of particular interest were the observations that wound healing could be accelerated in the 30-50% range with the dose response displaying biphasic characteristics consistent with the hormesis dose-response model.

Low dose radiation therapy (LD-RT) is effective in the treatment of arthritis: animal model findings.

Purpose: This paper provides a critical assessment of the hypothesis that low doses of ionizing radiation may be potentially effective in the treatment of inflammatory conditions, with particular focus on arthritis.

Materials And Methods: A critical review of the biomedical literature was undertaken to assess whether low doses of ionizing radiation may affect the progression of experimentally-induced arthritis using multiple animal models.

Results: The findings indicate that low doses of ionizing radiation were effective in alleviating the occurrence of clinical symptoms of arthritis in five complementary experimental models of arthritis.

Reduction of arthritic symptoms by low dose radiation therapy (LD-RT) is associated with an anti-inflammatory phenotype.

Purpose: The aim of this paper was to provide an integrative mechanistic appraisal to account for consistent observations of protective effects of ionizing radiation on the occurrence/ progression of arthritis in multiple animal models.

Materials And Methods: A critical analysis of the biomedical literature was undertaken to assess mechanisms by which low doses of ionizing radiation prevent and/or reduce the occurrence of experimental-induced arthritis in animal models.

Results: Detailed mechanistic-related research indicates that low doses of ionizing radiation induce a highly integrated multiple pathway process that results in the formation of a generalized anti-inflammatory phenotype which can both prevent the occurrence of arthritic changes and/or reverse such effects.

Hormesis: its impact on medicine and health.

This article offers a broad assessment of the hormetic dose response and its relevance to biomedical researchers, physicians, the pharmaceutical industry, and public health scientists. This article contains a series of 61 questions followed by relatively brief but referenced responses that provides support for the conclusion that hormesis is a reproducible phenomenon, commonly observed, with a frequency far greater than other dose-response models such as the threshold and linear nonthreshold dose-response models. The article provides a detailed background information on the historical foundations of hormesis, its quantitative features, mechanistic foundations, as well as how hormesis is currently being used within medicine and identifying how this concept could be further applied in the development of new therapeutic advances and in improved public health practices.

NEPA, EPA and risk assessment: Has EPA lost its way?

The EPA risk assessment practice denies the inclusion of beneficial responses in the evaluation process. This practice represents a marked deviation from the original guidelines set forth within NEPA, which required the integrated goal of environmental protection as including both a reduction in risk as well as an enhancement of health benefit. It is time for regulatory agencies such as EPA to incorporate both harm and benefit within its risk assessment process.