In the open access paper noted here, researchers use modeling to suggest that age-related decline of the thymus, and thus of the immune system, is more important than mutation as a determinant of cancer risk. Cancer is at root caused by mutational damage to DNA. While DNA repair and replication mechanisms are highly efficient, mutations nonetheless occur - and must occur at some rate in order for evolution to take place. It is a numbers game, in that the more time, the more cells, and the more cell activity, the greater the odds that a cancerous mutation will occur. Mutation rates are also affected by external factors such as radiation, toxic molecules in the cellular environment, and other forms of stress put upon cells. But this is just the primary cause, the trigger enables a cell to replicate without restraint.

After a mutation occurs, there are several classes of process that work to shut down or destroy potentially cancerous cells. We suffer countless potential cancers in our lives, but near all are suppressed before they start. The first line of defense is internal to cells: mechanisms such as those related to p53 that can respond to cancerous mutations and aberrant behavior by inducing immediate programmed cell death or inducing the state of cellular senescence. The latter shuts down replication, sets the cell on the path to self-destruction via apoptosis, and further issues signaling that calls in the immune system to destroy the errant cell. The immune system is the second, and perhaps more important line of defense. Immune cells of various types aggressively seek out and destroy cells that show signs of cancer or other undesirable behavior.

Unfortunately, the immune system declines in effectiveness with age. One of the reasons for this decline is a slowing of the rate at which new T cells are created. This is in part a question of the loss of stem cell activity that occurs throughout the body, reducing the generation of new cells of all sorts. Perhaps more important in the case of T cells is the age-related atrophy of the thymus, however. This organ is where T cells mature before taking up their assigned roles in the body. It is highly active in childhood, but the active tissue begins to be replaced by fat at the onset of maturity, a process called involution. This continues over a life span and into old age, and the pace at which new T cells mature falls along with it.

A slow rate of T cell replacement causes the existing specialized and active T cell populations to become ever more worn and ragged, lacking reinforcements that can respond effectively to new challenges. This affects most of the aspects of immune function, from the response to invading pathogens to the ability to catch and destroy cancerous cells before they start in earnest the process of generating a tumor. For this reason there is considerable interest in the research community in finding ways to rejuvenate the thymus, to restore the active tissue that acts as a nursery for T cell maturation. If successful, this should go some way towards regaining the lost capacity of the immune system.

Thymic involution and rising disease incidence with age