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55: The watershed age when cancer risk increases

July 23, 2020

Findings of a study published in Nature Genetics indicate that at age 55 decay kicks in
Repair of damaged DNA can no longer be sustained after this age
The emergence and persistence of mutations after age 55 increase the risk of dangerous diseases
The findings could pave the way to find ways to prevent cancer by identifying multiple mutated cell lines

The human body is not designed to live forever. But scientists have now concluded that decay sets in as early as age 55. At around this age, there is degeneration of DNA which the body cannot repair, increasing the risk of diseases like cancer. A large genetic study conducted by an international consortium, including a team of scientists from the State Serum Institute in Denmark, have published their results in Nature Genetics. “The study shows that our bodies are really good at repairing DNA damage until we reach the age of around 55,” explains Professor Mads Melbye, executive vice president at SSI and head of the Danish team. “After this point, our ability to fight off foreign or diseased cells starts to decline gradually.”

Aging and DNA Damage

Scientists around the world have mapped the human genome and studied the genetic code of individuals to try and find out why certain people have a higher risk of developing age-related diseases. This study is different in that it uses the technology to track how long the human body can effectively repair damaged DNA, also known as mutations. The objective of the study was to find out how long the body is capable of sustaining repair so that mutations don’t take control of the body. In other words, how long can humans retain control over their DNA? “In principle, the method makes it possible to gain an early indication of whether a person faces an increased risk of developing leukemia,” says Bjarke Feenstra, senior researcher in genetic epidemiology. Mutations are small changes in the DNA. However, if a mutation persists, it gives rise to a new line of cells that contain the altered DNA which are different from other cells in the body. Each of these cell lines is called a clone. The number of clones in a person’s body tells us how many injuries their DNA has sustained.

Mutations Trigger Dangerous Diseases

With age, the number of mutated cell lines increases because the body is unable to repair and combat the damage. Several cell lines combine to form what is called a mosaic. The presence of a mosaic increases a person’s risk of developing disease. New technology allows scientists to map mosaics within an individual’s DNA. During the new study, the researchers examined how this phenomenon occurs over a person’s lifespan. “The more mutated cells we allow to gain a foothold in our bodies, the greater the risk of one of these actually developing into a cancer,” says Melbye. “Until we reach the age of 55, it is not a problem. But after this point, a clear change starts to occur in our bodies. At this point, the body starts allowing significantly more new foreign cell clones to grow.” The scientists sampled DNA from people of different age groups to compare how many cell lines are typically present over a human lifetime. To accomplish this, the group needed access to massive amounts of data. They established the GENEVA consortium that obtained genetic data from 16 studies and a total of 50,000 individuals, making the analysis extremely reliable.

Old Age and Increase in Mosaics

The study included 4,000 samples from Danish mothers and their newborn babies. “Up to the age bracket of 55, less than half a percent of the subjects had a mosaic, i.e. more than one cell line,” says Feenstra. “After 55, there was a sharp increase in the percentage, reaching 3 percent at the age of 80, after which it remains constant.”

Paving the Way for Cancer Prevention

The researchers studied each person’s medical record and found that people with a mosaic had a 10 times higher chance of developing leukemia compared those without a mosaic. “In many cases, the mosaics overlapped regions of the genetic material that are known to contain mutations in people with leukemia,” says Feenstra. Although it is his personal opinion, Feenstra thinks this could pave the way to diagnose and prevent leukemia. “In principle, the method makes it possible to gain an early indication of whether a person faces an increased risk of developing leukemia,” he says. “However, there is still only a tiny share of people with a genetic mosaic who actually develop leukemia.”

Biological Causes of Cancer Remain a Mystery

The researchers working on this project focused on leukemia, but they believe it is a general phenomenon that applies to other types of cancer and other diseases. Additional research is needed to establish this, however, say Feenstra and Melbye. “Whether it’s our own ability to repair the DNA injuries that constantly occur in our bodies, which suddenly decreases around the age of 55, or whether it’s our own immune system that slowly loses the ability to destroy foreign cell lines in the body is a subject for future research,” says Melbye. One thing the new study has made clear in Melbye’s opinion is that our body is the best physician. It has an astonishing ability to stay healthy for at least five decades. “If we learn to understand what it is that changes when we reach the age of 55, we may be able to develop some form of therapy that postpones this point,” he says. “Such a procedure would most likely have a pronounced effect on the occurrence of certain forms of cancer and would delay the age at which they appear. This would mean an increased number of healthy years.”

References: https://sciencenordic.com/age-biotechnology-cancer/we-lose-control-of-our-dna-at-age-55/1371948