Hormesis: Toxicological foundations and role in aging research

Area of Science:

• Toxicology
• Biogerontology

Background:

• The threshold dose response model has been a cornerstone of toxicological assessment and regulatory procedures since the early 20th century.
• This model's predictive capacity, particularly in low-dose scenarios, remained largely unvalidated throughout the 20th century.

Observation:

• Recent investigations reveal significant failures of the threshold and linear dose response model in accurately predicting outcomes at low doses.
• Conversely, the hormetic dose response model, historically overlooked, demonstrated accurate predictions in low-dose zones during validation assessments.

Findings:

• The threshold model's inability to accurately predict low-dose responses represents a critical failure in toxicology.
• Hormetic dose responses have been increasingly documented in biogerontology research over the past two decades.
• The low-dose stimulatory effect of hormesis is linked to enhanced biological performance, improved aging quality, and extended lifespan in experimental models.

Implications:

• These findings have substantial public health, medical, and economic implications due to the widespread use of the flawed threshold model.
• Re-evaluation of toxicological models is necessary to incorporate hormetic effects for more accurate risk assessment.
• Understanding hormesis may unlock new strategies for promoting healthy aging and longevity.