Defining the toxicology of aging

Jessica A Sorrentino; Hanna K Sanoff; Norman E Sharpless

doi:10.1016/j.molmed.2014.04.004

Defining the toxicology of aging

Trends Mol Med. 2014 Jul;20(7):375-84. doi: 10.1016/j.molmed.2014.04.004. Epub 2014 May 28.

Authors

Jessica A Sorrentino¹, Hanna K Sanoff², Norman E Sharpless³

Affiliations

¹ The Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, 27599-7270, USA; The Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7295, USA.
² The Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7295, USA; Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7264, USA.
³ The Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC, 27599-7270, USA; The Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7295, USA; Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7264, USA; Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC, 27599-7264, USA. Electronic address: Norman_Sharpless@med.unc.edu.

Abstract

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.

Keywords: CDKN2a; biomarkers; gerontogen; p16(INK4a); senescence; toxicology.

Publication types

Review

MeSH terms

Aging / pathology*
Animals
Cellular Senescence / drug effects*
Cellular Senescence / physiology*
Environmental Pollutants / adverse effects*
Humans
Phenotype

Substances

Environmental Pollutants

Abstract

Publication types

MeSH terms

Substances

Grants and funding