At first glance aging and cancer appear to be unrelated. Aging is characterized by time-dependent decline of different physiological functions, while cancer represents the gain of new, undesired, cellular functionalities.
However, there is a strong correlation between age and cancer in humans. Aging is considered the single highest risk for developing cancer, and 60% of all malignant tumors occur in the age group 65 years and older. This age group is 11 times more likely to develop cancer than persons under age 65. This is a major concern in wealthy countries, where cancer is the second leading cause of death after heart disease.
There are 2 main hypotheses proposed to relate cancer and aging.
The first hypothesis considers the rise in the incidence of cancer with age as the time required by a cell to acquire multiple oncogenic, (or cancer causing), mutations. In other words, with age we increase the time of exposure to environmental carcinogens, thus increasing the number of mutations that accumulate in the genome. Oncogenic mutations provide a cell with new and aberrant phenotypes, considered essential hallmarks of cancer. The malignant properties of a cancer cell include uncontrolled cellular division with limitless replicative potential, resistance to anti-growth signals and programmed cell death, deregulated metabolism, and the capacity to invade surrounding tissues and spread to distant body parts.
Interestingly though, despite oncogenic mutations being a clear requirement for cancer initiation and progression, the majority of them accumulate during development rather than during adulthood. This is due to the lower rate of cell division after maturity, in part counteracted by a decreased capacity of cells to repair their DNA. If cancer is caused when a cell acquires 5 or 6 mutations, then a 20 year old should have high risks of getting cancer. So, why does our rate of getting cancer exponentially increase with age (Figure 1)?
The answer to this question might come from the second hypothesis: changes in the tissue environment support and drive cancer and other diseases of aging. A possible contributor to these changes is the decline of the immune system, which can become inefficient in clearing pathogens and damaged host cells.
These damaged cells, which accumulate with age, often react to stress insults by secreting factor to communicate their condition to the neighboring cells.
One example is cellular senescence. Senescence is a state of permanent growth arrest coupled with changes in metabolism and morphology. Senescent cells develop a very specific secretory phenotype that is called Senescence-Associated Secretory Phenotype, or SASP.
The secreted factors, from senescent cells or other cell types, can lead to the disruption of the tissue homeostasis and promote the formation of pro-cancer niche, rich of factors involved in different steps of tumourigenesis.
From a practical point of view, we should consider how environmental changes contribute to modify the tissue microenvironment thus favoring cancer formation and progression. As a preventive approach, maintaining healthier tissues, for example through a correct nutrition or physical activity, might lower cancer incidence with age. As a therapeutic approach, it will be interesting to consider the development of drugs that could ‘fix’ or eliminate seemingly normal cells that express aberrant but non-cancerous phenotypes, thus contributing to a pro-malignant tissue niche, and consider combinatorial treatments with drugs that target specific mutations in the cancer cells.