Hormesis: Toxicological foundations and role in aging research.

The field of toxicology adopted the threshold dose response in the early decades of the 20th century. The model was rapidly incorporated into governmental regulatory assessment procedures and became a central feature of chemical evaluation and assessment. The toxicological community never validated the capacity of this model to make accurate predictions throughout the remainder of the 20th century. A series of recent investigations have demonstrated that the threshold and linear dose response model failed to make accurate predictions in the low dose zone. Such findings demonstrate a profound failure by the toxicology community on the central pillar of its discipline and one with profound public health, medical and economic implications. Ironically, the hormetic dose response, which was rejected by the toxicology community during the early decades of the 20th century, accurately predicted responses in the low dose zone in the same three large-scale validation assessments. Within the past two decades hormetic dose responses have been frequently reported in the experimental biogerontology literature, associated with endpoints associated enhancing healthy aging and longevity. The low dose stimulatory response of the hormetic dose response model represents the quantification of enhanced biological performance in the experimental facilitation of aging quality via multiple endpoints and mechanisms and in the extension of lifespan in such animal models research.