This week on Lifespan News, Ryan O’Shea discusses a new CRISPR breakthrough, the creation of new neurons from astrocytes in vivo, the Dog Aging Project on Science to Save the World, serum albumin increasing lifespan in a mouse study, and the effects of hypoxia on the SASP.
The gene editing tool CRISPR has made headlines in recent years for its potential to eliminate diseases, enhance human abilities, and even create designer babies. But recent research demonstrates that CRISPR techniques may also help reprogram cells to a younger state. We’ll have this story and more in this episode of Lifespan News.
Welcome to Lifespan News on X10, your source for longevity science updates. I’m your host, Ryan O’Shea. As always, we encourage you to check the description below for links to these stories.
Continuing with our first story, scientists developed a new technique using CRISPR that makes it possible to switch genes on and off with greater precision and ease. All cells have the same genome, but not all genes are switched on, or expressed, in all cells. The epigenome, which you can think of as genetic “switches”, is different for different cell types, and it determines which genes are expressed and which aren’t. Epigenetic alterations are a primary hallmark of aging. As we age, our epigenome changes in unwanted ways, switching on or off the wrong genes. Scientists have been able to “reset” the epigenome in cells to a younger state for a while now, thanks to exposure to four chemicals known as Yamanaka factors; however, this process is complicated, requires precise timing, and is indirect in that exposure to Yamanaka factors pushes cells to use their internal machinery to reset the epigenome. The new technique, based on the popular CRISPR-Cas9 gene editing tool, enables directly changing the epigenome of cells, switching genes on or off at will. More specifically, the new technique allows to methylate or demethylate specific portions of the genome using single-guide RNA. In experiments, the technique performed very well, with over 80% of the targeted genes remaining silenced 50 days after the application. At the moment, this method is only useful in laboratory experiments on cells, and it’s going to be a while before it might be used to reset the epigenetic makeup of aged people to a younger state, but it’s still a breakthrough that will facilitate aging research.
For our next story, scientists managed to reprogram a type of brain cell known as astrocytes to become healthy neurons. The ability to regenerate tissue in mammals is rather poor, particularly in the brain, which can regenerate only in certain areas and only to a certain extent. Cellular reprogramming can be used to turn existing cells into cells of different types, which can be especially useful for the treatment of cognitive decline. Astrocytes are close relatives of neurons, and much more abundant in the brain. Their similarity with neurons makes them ideal candidates for conversion into neurons. The authors of the study used a previously experimented-on drug cocktail to see if it was able to turn astrocytes into neurons, both in vitro and in vivo. The experiment was performed on live adult mice, and after two weeks of treatment, the researchers were able to confirm that a considerable amount of new neurons had been formed, though it varied depending on brain regions. According to their analyses, the newly formed neurons were fully functional and fully integrated into the existing brains. As usual, the path from this experiment to the clinic will likely be long, but one day, it might be possible to use this technique to help people with brain damage or age-related cognitive decline.
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In a recent episode of Lifespan News, we discussed how the Dog Aging Project is studying aging in pet dogs, which may lead to treatments to slow it down or reverse it. Now, a new video has just been released by Science to Save the World which dives into this topic further and features interviews with the scientists leading this initiative. Make sure to visit their YouTube and Facebook page to watch Part 1, and subscribe so that you don’t miss Part 2!
Moving on, a recently published manuscript reports a 20% increase in the lifespan of middle-aged mice following a treatment with recombinant serum albumin. Serum albumin, a component of vertebrate blood plasma produced by the liver, is the most common blood protein in mammals. Because aging affects circulating blood factors, researchers hypothesized that diluting the damaged serum albumin in middle-aged mice might extend their lifespan. To test this, they gave 12-month old mice serum albumin injections every 3 weeks. This resulted in a 17.6% increase in female lifespan and a 20.3% increase in male lifespan. The treatment also improved grip strength and performance on a maze test. The researchers also reported that the treated mice had glossier and thicker fur than the control group. These results indicate that fresh albumin increases the lifespan of mice, supporting the notion that longevity can be promoted by restoring lost beneficial factors in aged blood or by reducing harmful factors. However, the exact mechanism behind the success of this treatment remains unclear. It’s also important to note that this reporting is based on a pre-print manuscript, so these findings have not yet been peer reviewed.
A new study suggests that the longevity benefits of hypoxia may result from suppression of the inflammatory senescence-associated secretory phenotype (SASP). In cell cultures, hyper-oxygenation accelerates cellular senescence, and extreme hypoxia has been found to reduce senescence and even put cells into an inactive state. In the new study, researchers compared cell cultures grown under normal oxygen levels and mild hypoxic conditions. They found that expression and secretion of multiple pro-inflammatory markers characteristic of the SASP were dramatically decreased in the hypoxic condition, suggesting that mild hypoxia may limit the most deleterious effects of cellular senescence. Inhibiting HIF-1α, a factor known to sense low oxygen conditions, was not sufficient to raise SASP levels in hypoxic cells, suggesting that other mechanisms were at play. The team then turned to mTOR, which was strongly expressed in normoxic conditions but absent in the hypoxic, non-senescent cells. Activation of mTOR restored the SASP in cells cultured under hypoxic conditions. The same was found for AMPK, indicating that the AMPK-mTOR pathway may mediate the link between hypoxia and SASP. This study helps illuminate how low oxygen levels could be beneficial to cells, which will be useful in trying to understand whether and how hypoxia is beneficial. The findings might also be useful in research on other pathways that interact with the SASP.
For our final story, a specific molecule could serve as a novel biomarker to test the performance of senolytics. In the past couple of years, some senolytic drugs — drugs that target senescent cells — have entered early clinical trials, but the lack of a simple biomarker to track senescence makes it difficult to evaluate them. Researchers surveyed the lipids in inactive, proliferating, and senescent human cells and detected a striking increase in the level of a class of lipids known as oxylipins. The oxylipin with the most elevated levels was a molecule called dihomo-15d-PGJ2. In a series of experiments, the team showed that this molecule accumulates inside senescent cells. When the senescent cells die, they release the molecule, and it can then be detected in blood plasma or urine samples. They also showed that the molecule could not be detected in mice treated with a senolytic drug. Finally, the researchers showed that the molecule is not only a marker of senescence but plays an active role in promoting it. Interfering with the synthesis of the molecule resulted in a fraction of the cells not becoming senescent, and treating non-senescent cells with the molecule induced senescence. The ability to easily monitor the efficacy of senolytics will be invaluable in clinical trials, and this biomarker could also be a useful tool for senescence research more broadly.
That’s all the news for this video. Before you go, there’s a few quick, free and simple things that you can do to help us solve the human aging problem. If you haven’t already, please make sure to like this video. Share this video on your social media. Please make sure that you’re subscribed with the bell turned to “All Notifications” to ensure you don’t miss any videos. Is there a recent life extension story that you think we should have included in one of our recent videos but haven’t yet? And which of the stories from this video excited you the most? Let us know what you think in the comments below. We really appreciate it and we look forward to seeing you in the next video at least as healthy as you are now.