“Essentially, the same investment in tissues that delays aging also delays cancer, based on our theory,” Dr DeGregori said. “The incidence curves for many human cancers are relatively similar, with 90% of all human cancers diagnosed in individuals over age 50. And yet, these cancers are initiating in very different stem cell pools of different sizes, and most importantly, these cancers are known to require different numbers of cancer-causing (oncogenic) events.”
For example, CML can involve a single genetic aberration, the BCR-ABL fusion, while colon cancers can require a stepwise accumulation of at least 4 oncogenic mutations, Dr DeGregori noted. The simple accumulation of mutations over time does not easily account for such patterns or the common incidence curves for human cancers.
But his and Dr Rozhok’s evolutionary physiological aging alternative to a chronological mutations-accumulation model of age-related cancer risk “implies that in older tissues, oncogenic mutations are more likely to be favored by intra-tissue selection,” added Dr Rozhok.
That implies that age-related vulnerability to cancer and other chronic diseases likely imposes a “hard ceiling” or intrinsic upper limit to potential lifespan for human beings, Dr DeGregori acknowledged, noting a recent estimate that this ceiling is approximately 115 years.
Many human cancers can be viewed as resulting from evolutionarily-novel environmental exposures against which we have not evolved molecular defenses, Dr DeGregori said. The main reason humans are particularly cancer-prone is that we live so long beyond our parenting years, he reiterated, “but we are also experiencing exposures that we did not evolve to deal with. The number one exposure is tobacco smoking, which is estimated to cause about one third of all cancer deaths.”
He also ticks off other examples: obesity, ultraviolet (UV) radiation exposure from sunlight, pollution, and alcohol.
But evolutionary models also allow something of a paradigm shift in our view of the cancer risks posed by carcinogens like tobacco smoke or alcohol: these exposures can hasten biological aging by disrupting molecular mechanisms for cellular homeostasis.
“Smoking clearly contributes to increasing cancer risk by increasing mutation frequency, but we argue that an even more important factor in cancer risk is that smoking majorly changes the tissue landscape,” Dr DeGregori explained.
Paul Ewald, PhD, is an evolutionary infectious disease biologist who directs the evolutionary medicine program at the University of Louisville in Kentucky. He commended DeGregori and Rozhok’s use of a Darwinian lens to better understand cancer epidemiology.
“We definitely want explanations based on evolutionary thinking because oncogenesis is an evolutionary process,” Dr Ewald noted. (He and others have been working on evolutionary frameworks for oncogenesis and the implications for tumor microenvironments for several years as well.5) “Accumulations of mutations are surely going to be part of the answer and I’d feel confident that the effects of reduced natural selection with advanced age are factors as well. Their argument is very appropriately based on principles of natural selection. Overall, their senescence theory explanation is very reasonable, but we have to be thinking about alternative explanations that are also consistent with evolutionary theory.”