Title: Intercellular competitive growth dynamics with microenvironmental feedback

Abstract: Normal life activities between cells rely crucially on the homeostasis of the cellular microenvironment, but aging and cancer will upset this balance. In this paper, we introduce the microenvironmental feedback mechanism to the growth dynamics of multicellular organisms, which changes the cellular competitive ability, and thereby regulates the growth of multicellular organisms. We show that the presence of microenvironmental feedback can effectively delay aging, but cancer cells may grow uncontrollably due to the emergence of the tumor microenvironment (TME). We study the effect of the fraction of cancer cells relative to that of senescent cells on the feedback rate of the microenvironment on the lifespan of multicellular organisms, and find that the average lifespan shortened is close to the data for non-Hodgkin lymphoma in Canada from 1980 to 2015. We also investigate how the competitive ability of cancer cells affects the lifespan of multicellular organisms, and reveal that there is an optimal value of the competitive ability of cancer cells allowing the organism to survive longest. Interestingly, the proposed microenvironmental feedback mechanism can give rise to the phenomenon of Parrondo's paradox: when the competitive ability of cancer cells switches between a too high and a too low value, multicellular organisms are able to live longer than in each case individually. Our results may provide helpful clues targeted therapies aimed at TME.