Why age matters when it comes to cancer
Scientists are beginning to understand why the risk of cancer increases as we age. It is now hoped that this will one day lead to new treatments.
King Charles Cancer diagnosis The past few days may have sent shockwaves around the world, not least because of the unusually frank revelations from Buckingham Palace. But many experts have seized the opportunity to raise awareness about rising cancer rates Risks faced by the elderly.
It has long been known that progressive progression over time is one of the biggest risk factors for developing cancer. According to the US National Cancer Institute, The average age of cancer onset is 66 yearswhile More than half Of all new cancer cases in the UK they are in people aged 70 and over.
There are many reasons for this. The first and simplest is that as we go through life, we gradually accumulate more damage to the DNA in our cells due to a wide range of factors. Some of the most common causes include exposure to ultraviolet radiation, chronic infections, environmental toxins, alcohol consumption, smoking, and microbial infections. But over time, our cells become less efficient In repairing this damage, leading to the accumulation of DNA mutations in a tissue-specific manner. The more mutations that accumulate in the body, the greater the risk of uncontrolled cell division, or cancer.
“Basically, repair mechanisms that may prevent changes that lead to cancer decline as we age,” says Richard Siu, director of aging research at King’s College London in the UK. “As we age, the balances that maintain normal cellular function decline.”
Studies have also found that these accumulated mutations weaken the ability of immune cells to suppress and destroy cancer cells. In particular, Masashi Narita, who researches cancer and aging at the University of Cambridge, points to a particularly well-known molecular pathway known as p53, which is involved in suppressing tumors. but, The effectiveness of this pathway decreases As we age, this is due to the accumulation of mutations in the p53 gene.
When various genetic mutations occur in blood stem cells, they cause them to gradually expand in size over time, something biologists have called Clonal hematopoiesis. This is very rare in young people but more common in older people, and can have two main consequences. The first is an increased risk of blood cancers, and the second is an alteration of the function of various immune cells such as monocytes, macrophages, and lymphocytes, which all originate from blood stem cells.
Narita and his research team experimented with several cancer-causing genetic mutations that become more common with age, to try to understand what happens to the human body. “We take one of these genes and introduce it into an adult animal and examine what happens at the single-cell level,” he says.
He and his team have already found that this appears to lead to a rise in cellular senescence, which is when old and damaged cells stop dividing and growing. The excessive accumulation of senescent cells can modify their surrounding environment in many harmful ways, leading to chronic inflammation that can cause further damage and increase susceptibility to cancer.
But these processes are still just a small handful of ways aging may affect cancer risk. Other new theories, stranger and more bizarre, are already beginning to emerge.
Cells lose their memory
Just as human memory declines with age, making us more forgetful and prone to lapses, some cancer biologists suspect that individual cells may also lose their memory over time and forget how to behave properly.
Luca Magnani, an epigeneticist at Cancer Research UK, says this is a valid theory for breast cancer, and is likely to result from hormonal changes that begin with menopause. According to To the NHS8 out of every 10 cases of breast cancer occur in women over the age of 50.
“A common hypothesis forming in the field is that these cells lose their memory and start replicating even if they’re not supposed to,” Magnani says.
One idea as to why this happens, not just in breast cancer but in many other age-related cancers, is that over the course of a lifetime, your genome becomes less stable at transmitting information. This is the result of so-called epigenetic changes or genetic modifications that affect gene activity without changing the DNA sequence.
“Information is transmitted in a less coherent and reliable way as you get older,” says Andy Feinberg, MD, professor of genetics and cancer at Johns Hopkins Medicine in Baltimore, Maryland. “There is more noise and this leads to more randomness or uncertainty about which gene pattern is supposed to be on and which is supposed to be off. It has been shown that the parts of the genome that have this increased noise are more likely to undergo oncogenic changes.”
But these ideas could also lead to entirely new ways of treating cancer. One of the most active areas in cancer drug development is small molecules that you are trying to address The deleterious effects of mutations in the p53 pathway and restoration of its normal tumor-suppressive functions.
Feinberg believes that the more we understand how epigenetics contributes to this increasing noise and randomness, the more we may be able to find ways to reverse these changes. “The encouraging thing is that the epigenetic changes are somewhat reversible,” he says.
Anti-Aging Scientists Early-stage clinical trials are currently underway Explore various chemical cocktails that selectively kill and remove senescent cells without harming healthy tissue. They are known as anti-aging agents, and they include an antioxidant called fisetin, a grape seed extract called polyphenol procyanidin C1, and a medication. Dasatinib In combination with another natural chemical called quercetin.
Right now, trials are testing some of these drugs in frail elderly individuals who have survived a previous battle with cancer to see if they can boost their immune function and overall health. If successful, it could have broader applications.
Seo is optimistic that research into newer treatment options that can reverse age-related changes and promote a person’s healthy lifespan — the number of years a person is healthy — could make a big difference in population health in the coming years.
“The goal is also to reduce the economic burden on health care,” he says. “…the care infrastructure will be very expensive because the population will live longer with the disease.”
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