Host age is a systemic regulator of gene expression impacting cancer progression

Cancer Res. 2015 Mar 15;75(6):1134-43. doi: 10.1158/0008-5472.CAN-14-1053. Epub 2015 Mar 2.

Abstract

Aging is the major determinant of cancer incidence, which, in turn, is likely dictated in large part by processes that influence the progression of early subclinical (occult) cancers. However, there is little understanding of how aging informs changes in aggregate host signaling that favor cancer progression. In this study, we provide direct evidence that aging can serve as an organizing axis to define cancer progression-modulating processes. As a model system to explore this concept, we employed adolescent (68 days), young adult (143 days), middle-aged (551 days), and old (736 days) C57BL/6 mice as syngeneic hosts for engraftment of Lewis lung cancer to identify signaling and functional processes varying with host age. Older hosts exhibited dysregulated angiogenesis, metabolism, and apoptosis, all of which are associated with cancer progression. TGFβ1, a central player in these systemic processes, was downregulated consistently in older hosts. Our findings directly supported the conclusion of a strong host age dependence in determining the host tumor control dynamic. Furthermore, our results offer initial mechanism-based insights into how aging modulates tumor progression in ways that may be actionable for therapy or prevention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging*
  • Animals
  • Cell Proliferation
  • Disease Progression
  • Gene Expression Regulation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / etiology*
  • Transforming Growth Factor beta1 / physiology

Substances

  • Transforming Growth Factor beta1