Effects of Aging on the Viscoelastic Properties of Tissues and Cancer Cell Behavior

Aging is accompanied by the declined biological functions of living organisms. Aging is a known risk factor for various diseases, including cancer. Though a vast body of studies have been reported regarding how aging-associated mutations lead to higher incidence of cancer development and more aggressive tumor progression in elder patients, few studies, if any, address how changing characteristics of the microenvironment in aging tissues might affect the course of cancer pathology. In addition, the systematic and quantitative comparison between young and aging tissues in humans or commonly used animal models is yet to be established. In this study, I hypothesized that aging epidermis, exhibiting distinct mechanical characteristics, promotes the progression of skin cancer in elder patients via p53-mediated pathways. First, to prove my hypothesis, I developed a versatile and economic device, coined indentation-based mechanical analyzer (IMA), to perform in situ and in vivo measurement of the viscoelastic properties of the human epidermis of different ages. We observed that both elastic moduli and viscosities of skin tissues increased with age using the old mouse and young mouse. Second, to systematically investigate how the altered viscoelasticity promotes tumor progression, I created an in vitro model system in mimicry of young and aging tissues. The in vitro model system will be used to evaluate the rate of tumor progression, drug responses, p53 activity and protein degradation in skin cancer cells growing in the varied viscoelastic environment. In summary, this study will advance the understanding of the complex relationship between aging and cancer, from the perspective of altered tissue mechanics and its consequences manifested in mechanosignaling-dependent regulations. Such understanding might inspire a distinct and more effective treatment strategy for elder cancer patients