This week on Lifespan News, Brent Nally introduces a test for multiple types of cancer, discusses how restricting blood flow in the brains of mice looks like brain aging, and brings up a new, safer method of cellular reprogramming developed by Calico scientists.
The biotech company GRAIL made history earlier this month by developing the first commercially available blood test able to detect several types of cancer. In other news, restricting blood flow caused young mice to express certain genes as if they were older, and Calico scientists developed safer cellular reprogramming. You’ll find these stories in this episode of Lifespan News.
Welcome to Lifespan News on X10, your source for longevity science updates. I’m your host, Brent Nally. We encourage you to check the description below for links to these stories. Lifespan News now has a couple new extra stories every week on X10’s parent YouTube channel Lifespan.io; so make sure you’re subscribed with the bell turned to all notifications so you don’t miss these videos.
For our first story, biotech company GRAIL recently introduced an early detection multi-cancer blood test that is now commercially available. Early cancer detection is extremely important for the sake of a patients’ survival chances; cancers that are detected at the earliest stages have much better survival rates compared to cancers spotted only later on. Unfortunately, only a few types of cancers have approved early detection methods, which are often invasive or uncomfortable, discouraging people from undergoing screenings. The new test created by GRAIL, called Galleri, addresses both problems at once, as it is able to detect dozens of cancer types with a simple blood test. Galleri works by analyzing the methylation pattern of circulating cell-free DNA, or cfDNA. cfDNA consists of degraded DNA molecules that have escaped from cells into the bloodstream. Cancer cells also shed cfDNA, and their specific methylation pattern can be recognised thanks to machine learning techniques. Galleri’s sensitivity across all cancer types ranged from 18% to 93%, depending on the stage of the cancer. Across a subset of highly prevalent cancers, sensitivity was even higher. The test was also able to predict the cancer’s tissue of origin with an accuracy of 96%. According to GRAIL themselves, Galleri is a tool that complements existing single-cancer screening methods rather than replacing them. Galleri is not yet perfect—for example, out of the 89% of prostate cancer cases detected by conventional methods, Galleri only detected 6%—but in many cases Galleri can make a huge difference. While tests are more easily approved than treatments, this is still a rare occurrence and therefore an impressive feat for GRAIL. We look forward to future improvements upon this technology.
We’ll try to keep you informed of the most recent and popular healthy life-extension podcasts. For this week, we recommend you check out Harvard professor of genetics David Sinclair returning to Joe Rogan’s podcast on Spotify.
For our next story, restricting blood flow caused young mice to express certain genes as if they were older. A study in mice has outlined the similarities between artificially restricted cerebral blood flow and the reduced blood flow associated with aging. The researchers used microcoils to reduce the amount of blood available to the brain, a procedure known as BCAS. This procedure reduced the cerebral blood flow in young mice nearly exactly to that of old mice, taking away roughly 30% of their cerebral blood flow and thus brain oxygen. This created substantial changes to their gene expression, particularly after 30 days. These genes included many critical functions of neurons along with fundamental metabolic processes, as their brains struggled to perform their function in a low-oxygen environment. The blood flow of older mice was also reduced by this procedure, but they changed their gene expression substantially less than young mice did, and their blood flow returned closer to its normal level. The researchers noted that young mice subjected to BCAS and normal old mice had similar expression levels of genes related to mitochondrial oxidation, the production of NAD+ from NADH, and the basic synthesis of ATP. This begs the question of how much of aging is caused by macro-scale physical processes that are caused by other aspects of aging. These results suggest this sort of causal chain: as some processes of aging cause ischemia, this limits critical oxygen flow to the brain, thus resulting in fewer neuroprotective proteins and increased mitochondrial dysfunction.
For our final story, Calico scientists developed safer cellular reprogramming. Calico’s discoveries about OSKM and pluripotency shed new light on an old problem. In a recent preprint, scientists from the secretive longevity research company Calico describe a possible way to make cellular reprogramming safer. Calico was founded in 2013 and is a subsidiary of Google’s parent company Alphabet. This new study is one of the few that have been publicly featured since Calico’s creation and is probably one of their most important. Cellular reprogramming is a technique that rejuvenates older cells back to a younger state of pluripotency. This means that reprogrammed cells lose their specialised identity and go back to a much earlier stage of development, where they can turn into essentially any type of cell. This is achieved by exposure to a cocktail of chemicals known as Yamanaka factors. Exposure to the four factors, indicated by the acronym OSKM, resets cellular identity and makes aged cells effectively younger, but this comes with a very bad downside: reprogrammed cells tend to acquire carcinogenic mutations. In other words, these cells can lead to cancer. To get around this problem, earlier efforts have focused on limiting the exposure to these four factors. Using this modified technique, termed transient reprogramming, scientists managed to achieve the benefit of traditional cellular reprogramming, but without sending cells all the way back to a pluripotent state, or so it was thought. Calico scientists found out that transient reprogramming does seem to bring cells back to a pluripotent state, albeit only partly or temporarily. Transiently reprogrammed cells tend to reacquire their identity shortly after the procedure, but this means that the possibility of carcinogenic mutations can’t be fully ruled out, which would make using the technique in vivo dangerous. It is known that some Yamanaka factors are more oncogenic than others, so Calico researchers wanted to see whether any could be left out. They found out that the answer was yes, and that even by leaving some factors out, it was possible to significantly rejuvenate cells without suppressing cellular identity as much as exposure to the full OSKM array does. The researchers did find out that some features of aging were apparently not affected by transient reprogramming, so as always, more research is needed.
That’s all the news for this episode. Is there a recent life extension story that you think we should have covered but haven’t yet? And what was your favorite story from this episode? Let us know what you think in the comments below and we’ll see ya in the next episode.