A new study in 2022 reveals a thought-provoking relationship between how long animals live and how quickly their genetic codes mutate. Cancer is a product of time and mutations, and so researchers investigated its onset and impact within 16 unique mammals. A new perspective on DNA mutation broadens our understanding of aging and cancer and lifespan development—and how we might be able to control it.
Mutations, Aging, and Cancer: A Primer
Cancer is the uncontrolled growth of cells. It is not a pathogen that infects the body, but a normal body process gone wrong.
Cells divide and multiply in our bodies all the time. Sometimes, during DNA replication, tiny mistakes (called mutations) appear randomly within the genetic code. Our bodies have mechanisms to correct these errors, and for much of our youth we remain strong and healthy as a result of these corrective measures.
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However, these protections weaken as we age. Developing cancer becomes more likely as mutations slip past our defenses and continue to multiply. The longer we live, the more mutations we carry, and the likelihood of them manifesting into cancer increases.
A Biological Conundrum
Since mutations can occur randomly, biologists expect larger lifeforms (those with more cells) to have greater chances of developing cancer than smaller lifeforms.
Strangely, no association exists.
It is one of biology’s biggest mysteries as to why massive creatures like whales or elephants rarely seem to experience cancer. This is called Peto’s Paradox. Even stranger: some smaller creatures, like the naked mole rat, are completely resistant to cancer.
This phenomenon motivates researchers to look into the genetics of naked mole rats and whales. And while we’ve discovered that special genetic bonuses (like extra tumor-suppressing genes) benefit these creatures, a pattern for cancer rates across all other species is still poorly understood.
Cancer May Be Closely Associated with Lifespan
Researchers at the Wellcome Sanger Institute report the first study to look at how mutation rates compare with animal lifespans.
Mutation rates are simply the speed at which species beget mutations. Mammals with shorter lifespans have average mutation rates that are very fast. A mouse undergoes nearly 800 mutations in each of its four short years on Earth. Mammals with longer lifespans have average mutation rates that are much slower. In humans (average lifespan of roughly 84 years), it comes to fewer than 50 mutations per year.
The study also compares the number of mutations at time of death with other traits, like body mass and lifespan. For example, a giraffe has roughly 40,000 times more cells than a mouse. Or a human lives 90 times longer than a mouse. What surprised researchers was that the number of mutations at time of death differed only by a factor of three.
Such small differentiation suggests there may be a total number of mutations a species can collect before it dies. Since the mammals reached this number at different speeds, finding ways to control the rate of mutations may help stall cancer development, set back aging, and prolong life.
The Future of Cancer Research
The findings in this study ignite new questions for understanding cancer.
Confirming that mutation rate and lifespan are strongly correlated needs comparison to lifeforms beyond mammals, like fishes, birds, and even plants.
It will also be necessary to understand what factors control mutation rates. The answer to this likely lies within the complexities of DNA. Geneticists and oncologists are continuing to investigate genetic curiosities like tumor-suppressing genes and how they might impact mutation rates.
Aging is likely to be a confluence of many issues, like epigenetic changes or telomere shortening, but if mutations are involved then there may be hopes of slowing genetic damage—or even reversing it.
While just a first step, linking mutation rates to lifespan is a reframing of our understanding of cancer development, and it may open doors to new strategies and therapies for treating cancer or taming the number of health-related concerns that come with aging.