Oxford Mathematician Sam Palmer tackles a crucial issue in our understanding of the risks of serious diseases such as cancer.
"Why does the risk of cancer and infectious diseases increase with age? For cancer, there are two main contributers: the declining immune system, and the accumulation of genetic mutations. My research points to immune system decline as the larger factor, in particular for cancers such as chronic myeloid leukemia and brain cancers. These cancers, along with many infectious diseases, rise exponentially with age at the same rate that the thymus shrinks. The thymus is where T-cells are produced and it involutes exponentially, starting from childhood, at a rate of 4% per year, resulting in a decline in T-cell production at the same rate.
To explain the observation that disease risk is often inversely proportional to T-cell production, we constructed a minimal mathematical model, which implicates rare stochastic growth and T-cell exhaustion as a rate limiting step in disease progression. This fits with the recent cancer immunotherapy renaissance, where targetting T-cell exhaustion has been hugely successful. Unexpectedly, our model can also explain the rise in cancer risk with age for more common cancers, such as colon and skin cancer, where risk does not rise exponentially, but rather as a power law. The fact that common cancers rise as power laws (usually proportional to age to the power of 5 or 6) has traditionally been viewed as evidence for the mutation-accummulation hypothesis; however our model shows that this behaviour also fits with the immune-decline hypothesis.
Now, I am working on thymus regeneration and using bioinformatics and mathematical modelling to try to understand the gene regulatory networks responsible for cell fate decisions in the thymus. "