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When you think about getting older, charming side effects like sore joints, wrinkles, or a toothless smile might come to mind. And while there are maybe some things to look forward to, like that AARP membership, it might not seem to balance out entirely. There may be one other advantage, however. At a certain point of aging, our risk of cancer starts going down. And if you're getting hung up on the idea that cancer is an old folks' disease, I mean, kinda. But keep watching. Because just like with all things in cancer, it is not that simple. [♪ INTRO] So cancer is one of those diseases that can strike anyone, regardless of age, though it tends to be more likely in older folks.
And there are a lot of things that can affect the risk of different cancers. We know that a lot of cancer risk can be affected by genetic factors, such as certain variants of the BRCA1 gene increasing the risk of breast cancer. That's why they call it brack-uh, B-R-C-A. It stands for BReast CAncer Environmental factors can also play a role, like smoking for lung cancer. But so can plain dumb chance. You can have no genetic risks and avoid things like smoking and too much sunlight, and still develop cancer. And that's because as your cells divide, which they're doing all the time, they can make some mistakes.
A lot of those mistakes are harmless. Maybe one DNA letter changed but in a place where it didn't make any difference, or maybe that mutation caused the cell to die, so it didn't start mass producing the mistake. But the more your cells divide, over the course of a few decades, the more likely it is to get one of the bad mutations, or to accumulate enough mutations where you start showing symptoms of a disease. That's a big part of why cancer is generally more likely as you age. Plus, you have more time to be exposed to environmental risk factors, your immune system usually weakens, and your body isn't as good at repairing DNA.
All of that spells more cancer for old people. So it makes sense that when you look at cancer incidence, it pretty much increases with age. …Until you get to the very oldest people. At some point, it looks like cancer incidence starts to actually go back down. A paper from 2017 found that this happened in the "oldest-old" group, which is anyone 85 years or older. That's a little strange because, theoretically, that group has had the most time to hoard those
random mutations, rub shoulders with carcinogens like tobacco or the sun, and power down their immune systems from regular ol' aging. With all those factors working in favor of tumor development, some researchers aren't convinced that the cancer decline is legit. It might be the incidence only looks like it goes down because it isn't being detected in that age group. There are some good reasons why that could be happening. Detecting cancer isn't always the most comfortable experience. At 95, a colonoscopy might not feel like it's worth the trouble, especially with how grueling the prep can be. Though if you are under 95,
I am here to tell you that colonoscopies aren't as bad as they're made out to be. If your doctor says do it, please do it. Additionally, if an individual is too frail or has chronic conditions, they might not be a candidate for certain procedures. And if the procedure requires anesthesia, the medical team may have to consider the risks and benefits of detecting that cancer. Plus, someone in their 90s might not care to know whether they have cancer or not, because they are adamant about not doing intensive treatments like chemo or surgery. At that stage of life, you might want to consider quality over quantity.
It could also be that the individuals prone to cancer already got it and succumbed to it earlier in life, leaving most of the oldest-old cancer-free. A kind of natural selection bias. But even though those things could affect how we understand cancer incidence in old folks, the consensus among epidemiologists today is that the decreased incidence of cancer among the oldest-old is real. So researchers out of Stanford and UPenn asked, what gives? And their 2025 paper suggests that there might be something on the molecular level working to older folks' advantage when it comes to cancer.
But before we get to that, we need to keep the lights on with this quick break. If you made it this far, you're probably the kind of person who loves engaging with new ideas and learning outside of a classroom. That's what we offer at SciShow, and it's what Brilliant offers too! You can enjoy all the good edu-tainment that you get from watching videos like SciShow plus a more interactive platform in Brilliant. Brilliant is made for everyone from age 10 to 110. And they're this video's sponsor. Brilliant helps you build skills and improve confidence in coding through courses like Programming with Functions.
To learn for free on Brilliant for a full 30 days, go to brilliant.org/scishow, scan the QR code onscreen, or click on the link in the description. Brilliant's also given our viewers 20% off an annual Premium subscription, which gives you unlimited daily access to everything on Brilliant. The researchers started where a lot of researchers do: with a bunch of mice. They split the mice into two groups, young and old, which translated to spry 5 month old mice versus geriatric mice closer to 21 months old.
The oldest old mice! Then they used gene editing to give both groups of mice lung cancer. For anyone who isn't a molecular biologist, that means identifying a gene that, when changed just a smidgen, can pretty much guarantee cancer will develop by doing things like eliminating all the cellular division checks and balances. It's like a company suddenly fired their entire quality control team. Something would probably go really wrong, really quickly. Genes that can easily cause tumor-inducing disaster with just a tiny change are called oncogenes. And the oncogene these scientists messed with was KRAS, whose mutations are one of the most
common linked to any cancer involving a solid tumor, including lung cancer. So they took that cancer prone version of KRAS, and put it in a virus, and then they delivered the virus into the mice's lungs so that it would spread the mutated gene to their lung cells and induce a lung tumor. Inducing the cancer was important so that everyone was on a level playing field. Rather than having the elderly mice having a cancer built on a lifetime's worth of mutations and the youngins' cancer caused by just one very unfortunate mutation, inducing the tumors made everyone start with genetically identical cancer.
But that cancer did not stay identical for long, because after giving the cancer 15 weeks to do its thing, the young mice had worse tumors than the older mice. Specifically, the aged mice had 2 to 3 times fewer tumor growths than the young mice, and four to five times fewer cancerous cells in general. And the size of the tumors was noticeably different too, with the older mice having significantly smaller tumors than the younger mice. Fewer tumors means some of the cancer was prevented from even starting, while the smaller tumors means their growth was also inhibited.
It's as if the older mice had some sort of beneficial effect that was basically weeding and pruning their cancer. At first, researchers thought that maybe the virus didn't get into the cells of the older mice as well as it did the young mice. So being very clever scientists, they added a glowing marker to the virus, injected it into the mice again, and played spot the difference between the old and the young mice. Except it wasn't a very good game, because the glowiness in the tissues among both groups was pretty much the same. That means the virus, with its cancer-happy version of the KRAS, was getting into the cells
equally as well, but something else was limiting the subsequent cancer development and growth. The next idea was that there might be a tumor suppressor gene working better in the older mice than in the younger mice. A tumor suppressor being the opposite of an oncogene - a gene that protects cells from cancer. And that would make sense, but the researchers found the opposite was true. One of the ways a mutated KRAS gene can cause tumors is by activating the PI3K-AKT pathway. We're getting deep in the weed now, everybody!
This is a specific signaling pathway, which is a cascade of little chemical messages between molecules that trigger functions in a cell. This specific pathway tells cells to divide and not die, which is why it plays a big role in tumor development. And that is where tumor suppressor genes come in, because leaving that pathway unchecked would be bad news for people who prefer to not have cancer. The scientists looked at a bunch of tumor suppressor genes, but the one that really caught their eye was the PTEN gene. That gene is really good at slowing down the PI3K-AKT pathway.
The idea was that if aged mice have smaller and fewer tumors, then this gene was probably working overtime to make that happen. And they did see a difference in how effective the tumor suppressor genes were in old mice versus young mice. Except, not in the direction they expected. When they knocked out the PTEN gene, tumors in the younger group grew over two times more than those in the older group, even though PI3K signaling increased in both. Knocking out genes is something molecular biologists do to find out what goes wrong when they're missing. So this result makes it seem like PTEN is doing more work in younger cells compared to older ones.
The effect of several other tumor suppressor genes also decreased with age. So those lazy tumor suppressor genes weren't to thank for the smaller tumors in older mice either, since they were apparently more active in the younger mice. But that experiment does suggest that something in the PI3K-AKT pathway gets less effective with age, which might partially explain the smaller tumors. The researchers also noticed that when they knocked out the PTEN gene in the older mice, the cancer cells looked younger, which is weird since no PTEN should mean more PI3K-AKT signalling, which would force cells to keep living even when they're super old.
All of those surprising findings means the researchers did not find the answer as to why the oldest-old have a decreased risk of cancer, and highlights why your grandparents really deserve to be included in more research. But those researchers aren't the only ones who have tried to suss out this situationship between aging and cancer. A paper from 2003 presented some reasons why tumors might be at a disadvantage when they target older folks. One idea proposed is that you're less likely to be exposed to carcinogens during your golden years. Somewhere between 2 and 8% of cancers are caused by exposure to carcinogens while you're on the job.
By the time you're 80, there's a pretty good chance that you have retired, so if you were being exposed to hazardous substances, you probably aren't anymore. And if you're in an assisted living or nursing facility, there are probably fewer environmental carcinogens like tobacco. A lot of the environmental changes associated with aging could mean less exposure to carcinogens, so a lower incidence of cancer would make sense. But that 2003 paper clocked some physiological reasons why the incidence might decrease with age too. As you age, your cells slow down in a lot of ways, including the speed at which they divide. That goes for healthy cells and unhealthy cells alike, such as tumor cells.
So for that mouse experiment, it might not be too surprising to see the older mice with smaller tumors, because it might just take longer for their tumor cells to divide and grow. All of the cells suck when you're old. But that only explains why the tumors would be smaller, not why there would be fewer of them. And for that, the authors credit a population of cells called senescent cells. Senescent cells are cells that are done multiplying but are not dying. They're essentially permanent retirees, and as you age, you build up more and more of them.
The key point is that they are done replicating, which means they can't be compelled out of retirement even if they're infected with a weird pro-cancer virus gene thingie made in a lab. Older folks have more of these cells that are essentially immune to becoming cancerous, which could explain why the older mice had fewer tumors. It's important to note that those cells can also release chemicals that increase the risk of cancer, so this isn't a clean cut Scooby Doo mystery with a single right answer.
Took his mask off. "It's you, the Senescent Cells! You're so old!" Both cancer biology and aging are complicated and deserve far more attention. But as we do learn more about the relationship between aging and cancer, this kind of research could guide more tailored treatment across the lifespan. Like, perhaps treatments targeting PTEN would be more effective in older folks since it seems like that gene gets a bit lazy with age. Or maybe further research will identify a gene or pathway that really does help older people fight off cancer better, and it can be used in treatment for younger cancer patients.
All of that starts with including more older people in cancer research, especially since they have historically been underrepresented in those studies. And in recent years, the FDA has even issued statements telling researchers to do as much. Not only is that a win for science in the spirit of inclusion and learning more, but it might even mean a few more of those golden years, if not for meemaw, then maybe someday for you. [♪ OUTRO]
