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  3. Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research

Chemically induced carcinogenesis in rodent models of aging: assessing organismal resilience to genotoxic stressors in geroscience research

  • Geroscience. 2019 Apr;41(2):209-227. doi: 10.1007/s11357-019-00064-4.
Anna Csiszar 1 2,  Priya Balasubramanian 1,  Stefano Tarantini 1,  Andriy Yabluchanskiy 1 2,  Xin A Zhang 3,  Zsolt Springo 1 4,  Doris Benbrook 2 5,  William E Sonntag 1 6,  Zoltan Ungvari 7 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Geriatric Medicine Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA.
  • 2 Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • 3 Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • 4 Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary.
  • 5 Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • 6 Department of Biochemistry, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
  • 7 Department of Geriatric Medicine Vascular Cognitive Impairment and Neurodegeneration Program, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 1311, Oklahoma City, OK, 73104, USA. [email protected].
  • 8 Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. [email protected].
  • 9 Theoretical Medicine Doctoral School, University of Szeged, Szeged, Hungary. [email protected].
  • 10 Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary. [email protected].
  • 11 Department of Public Health, Semmelweis University, Budapest, Hungary. [email protected].
PMID: 31037472 DOI: 10.1007/s11357-019-00064-4
Abstract

There is significant overlap between the cellular and molecular mechanisms of aging and pathways contributing to carcinogenesis, including the role of genome maintenance pathways. In the field of geroscience analysis of novel genetic mouse models with either a shortened, or an extended, lifespan provides a unique opportunity to evaluate the synergistic roles of longevity assurance pathways in Cancer resistance and regulation of lifespan and to develop novel targets for interventions that both delay aging and prevent carcinogenesis. There is a growing need for robust assays to assess the susceptibility of Cancer in these models. The present review focuses on a well-characterized method frequently used in Cancer research, which can be adapted to study resilience to genotoxic stress and susceptibility to genotoxic stress-induced carcinogenesis in geroscience research namely, chemical carcinogenesis induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA). Recent progress in understanding how longer-living mice may achieve resistance to chemical carcinogenesis and how these pathways are modulated by Anti-aging interventions is reviewed. Strain-specific differences in sensitivity to DMBA-induced carcinogenesis are also explored and contrasted with mouse lifespan. The clinical relevance of inhibition of DMBA-induced carcinogenesis for the pathogenesis of mammary adenocarcinomas in older human subjects is discussed. Finally, the potential role of insulin-like growth factor-1 (IGF-1) in the regulation of pathways responsible for cellular resilience to DMBA-induced mutagenesis is discussed.

Keywords

Cancer; Carcinoma; DNA repair; Health span; Mutagenesis; Mutation; Tumor.

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