Defining the toxicology of aging

• Exposures to certain toxicants (‘gerontogens’) can accelerate physiological aging.
• Unequal exposures to gerontogens may cause people to age at different rates.
• Markers of senescence show promise as biomarkers to quantify gerontogenic exposures.

Mammalian aging is complex and incompletely understood. Although significant effort has been spent addressing the genetics or, more recently, the pharmacology of aging, the toxicology of aging has been relatively understudied. Just as an understanding of ‘carcinogens’ has proven crucial to modern cancer biology, an understanding of environmental toxicants that accelerate aging (‘gerontogens’) will inform gerontology. In this review, we discuss the evidence for the existence of mammalian gerontogens, as well as describe the biomarkers needed to measure the age-promoting activity of a given toxicant. We focus on the effects of putative gerontogens on the in vivo accumulation of senescent cells, a characteristic feature of aging that has a causal role in some age-associated phenotypes.