Host age is a systemic regulator of gene expression impacting cancer progression.
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.
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, Massachusetts.
Afshin
A
Beheshti
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, Massachusetts. INRIA Bordeaux Sud-Ouest MC2, Talence, France.
Sébastien
S
Benzekry
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, Massachusetts.
J Tyson
JT
McDonald
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, Massachusetts.
Lili
L
Ma
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, Massachusetts.
Michael
M
Peluso
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, Massachusetts.
Philip
P
Hahnfeldt
Center of Cancer Systems Biology, Tufts University School of Medicine, Boston, Massachusetts. Hlatky@cancer-systems-biology.org.
Lynn
L
Hlatky
D000367:Age Factors; D000375:Aging; D000818:Animals; D049109:Cell Proliferation; D018450:Disease Progression; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000209:etiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology
D053773:Transforming Growth Factor beta1