California researchers develop drug cocktail that reverses aging — results 'remarkably promising'
Scientists find promising results in trial to reverse biological aging.
- Volunteers given a mix of three drugs "aged backwards," shedding 2.5 years off their biological ages.
- The research focused on marks on their DNA and epigenetic clock.
- Scientists need to continue this research with a larger population size for their next trial.
A recent minor clinical study in California suggests that for the first time ever, it may be possible to reverse the body's biological epigenetic clock.
Over the course of a year, nine healthy participants were given a mixture of three common drugs, which included a growth hormone and two diabetes medications. On average, it was found that 2.5 years of their biological ages had been shed after analyzing their genomes. Additionally, their immune systems showed signs of rejuvenation.
The results surprised researchers, but the scientists cautioned that these findings are only preliminary as the trial wasn't large enough and didn't have a control group.
Reversal of biological aging study
Clinical researchers tested the blood samples taken from the trial in order to review the reversed aspects of human aging. The significant reversal in their epigenetic ages was astounding. While they'll need to follow this study with more rigorous and large scale trials in the future, they still remain optimistic that a person's biological age can be reversed.
Their findings were published in the research journal Aging.
The authors stated that,". . . epigenetic age does not measure all features of aging and is not synonymous with aging itself, it is the most accurate measure of biological age and age‐related disease risk available today."
The results of their study put forth preliminary evidence that regression of multiple areas and markers of aging will be one day be possible for humans. The researchers write:
"The present study now establishes highly significant evidence of thymic regeneration in normal aging men accompanied by improvements in a variety of disease risk factors and age‐related immunological parameters."
What is epigenetic age?
The epigenetic clock is based off of the body's epigenome, which is comprised of the chemical modifications that occur and tag DNA, usually found on methyl groups. Patterns of these tags change during your life as you age. Scientists use these markers to track a person's biological age, sometimes they either exceed or fall behind someone's chronological age.
Scientists create epigenetic clocks by selecting certain sets of DNA-methylation site across a person's genomes.
The latest trial was created in order to test whether growth hormone could be safely used to restore human tissue in the thymus gland, this has already successfully been done in trials on dogs and rats.
The thymus gland is located in the chest between your lungs and breastbone. It serves a crucial function for the immune system. White blood cells that are produced in bone marrow mature inside the thymus, where they turn into T cells that help fight infection. This gland begins to gradually shrink after puberty.
Evidence from previous animal trials and some small human studies have suggested that the growth hormone can regenerate the thymus. However, growth hormone can also produce diabetes.
This is why the trial added two anti-diabetic drugs in the reversal aging cocktail, which consisted of dehydroepiandrosterone (DHEA) and metformin.
A scientific first that requires further investigation
University of California Los Angeles (UCLA) geneticist, Steve Horvath, one of the researchers involved in the study and a pioneer in the human aging epigenetic research told the journal Nature that he was surprised by the results.
"I'd expected to see slowing down of the clock, but not a reversal. That felt kind of futuristic," he said. "This told me that the biological effect of the treatment was robust." The effect stayed in the participants blood samples some six months after the trial was finished.
The authors wrote, ""Epigenetic 'clocks' can now surpass chronological age in accuracy for estimating biological age. This is to our knowledge the first report of an increase, based on an epigenetic age estimator, in predicted human lifespan by means of a currently accessible aging intervention."
According to the researchers, further studies must be conducted to fully confirm and build on these findings. They've found that as the thymus shrinks in older aged individuals, critical immune cell populations result in the collapse of T-cell receptors (TCR). This connects with and leads to most causes of death in the elderly, which include age-related increases in cancer, lowered immunity to infectious diseases, autoimmune disorders and more.
The study's authors end on a final note that, "Although much more remains to be done. The general prospects for meaningful amelioration of human aging appear to be remarkably promising."
Join Radiolab's Latif Nasser at 1pm ET today as he chats with Malcolm Gladwell live on Big Think.
Astronomers find these five chapters to be a handy way of conceiving the universe's incredibly long lifespan.
- We're in the middle, or thereabouts, of the universe's Stelliferous era.
- If you think there's a lot going on out there now, the first era's drama makes things these days look pretty calm.
- Scientists attempt to understand the past and present by bringing together the last couple of centuries' major schools of thought.
The 5 eras of the universe<p>There are many ways to consider and discuss the past, present, and future of the universe, but one in particular has caught the fancy of many astronomers. First published in 1999 in their book <a href="https://amzn.to/2wFQLiL" target="_blank"><em>The Five Ages of the Universe: Inside the Physics of Eternity</em></a>, <a href="https://en.wikipedia.org/wiki/Fred_Adams" target="_blank">Fred Adams</a> and <a href="https://en.wikipedia.org/wiki/Gregory_P._Laughlin" target="_blank">Gregory Laughlin</a> divided the universe's life story into five eras:</p><ul><li>Primordial era</li><li>Stellferous era</li><li>Degenerate era</li><li>Black Hole Era</li><li>Dark era</li></ul><p>The book was last updated according to current scientific understandings in 2013.</p><p>It's worth noting that not everyone is a subscriber to the book's structure. Popular astrophysics writer <a href="https://www.forbes.com/sites/ethansiegel/#30921c93683e" target="_blank">Ethan C. Siegel</a>, for example, published an article on <a href="https://www.forbes.com/sites/startswithabang/2019/07/26/we-have-already-entered-the-sixth-and-final-era-of-our-universe/#7072d52d4e5d" target="_blank"><em>Medium</em></a> last June called "We Have Already Entered The Sixth And Final Era Of Our Universe." Nonetheless, many astronomers find the quintet a useful way of discuss such an extraordinarily vast amount of time.</p>
The Primordial era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTEyMi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNjEzMjY1OX0.PRpvAoa99qwsDNprDme9tBWDim6mS7Mjx6IwF60fSN8/img.jpg?width=980" id="db4eb" class="rm-shortcode" data-rm-shortcode-id="0e568b0cc12ed624bb8d7e5ff45882bd" data-rm-shortcode-name="rebelmouse-image" />
Image source: Sagittarius Production/Shutterstock<p> This is where the universe begins, though what came before it and where it came from are certainly still up for discussion. It begins at the Big Bang about 13.8 billion years ago. </p><p> For the first little, and we mean <em>very</em> little, bit of time, spacetime and the laws of physics are thought not yet to have existed. That weird, unknowable interval is the <a href="https://www.universeadventure.org/eras/era1-plankepoch.htm" target="_blank">Planck Epoch</a> that lasted for 10<sup>-44</sup> seconds, or 10 million of a trillion of a trillion of a trillionth of a second. Much of what we currently believe about the Planck Epoch eras is theoretical, based largely on a hybrid of general-relativity and quantum theories called quantum gravity. And it's all subject to revision. </p><p> That having been said, within a second after the Big Bang finished Big Banging, inflation began, a sudden ballooning of the universe into 100 trillion trillion times its original size. </p><p> Within minutes, the plasma began cooling, and subatomic particles began to form and stick together. In the 20 minutes after the Big Bang, atoms started forming in the super-hot, fusion-fired universe. Cooling proceeded apace, leaving us with a universe containing mostly 75% hydrogen and 25% helium, similar to that we see in the Sun today. Electrons gobbled up photons, leaving the universe opaque. </p><p> About 380,000 years after the Big Bang, the universe had cooled enough that the first stable atoms capable of surviving began forming. With electrons thus occupied in atoms, photons were released as the background glow that astronomers detect today as cosmic background radiation. </p><p> Inflation is believed to have happened due to the remarkable overall consistency astronomers measure in cosmic background radiation. Astronomer <a href="https://www.youtube.com/watch?v=IGCVTSQw7WU" target="_blank">Phil Plait</a> suggests that inflation was like pulling on a bedsheet, suddenly pulling the universe's energy smooth. The smaller irregularities that survived eventually enlarged, pooling in denser areas of energy that served as seeds for star formation—their gravity pulled in dark matter and matter that eventually coalesced into the first stars. </p>
The Stelliferous era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTEzNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMjA0OTcwMn0.GVCCFbBSsPdA1kciHivFfWlegOfKfXUfEtFKEF3otQg/img.jpg?width=980" id="bc650" class="rm-shortcode" data-rm-shortcode-id="c8f86bf160ecdea6b330f818447393cd" data-rm-shortcode-name="rebelmouse-image" />
Image source: Casey Horner/unsplash<p>The era we know, the age of stars, in which most matter existing in the universe takes the form of stars and galaxies during this active period. </p><p>A star is formed when a gas pocket becomes denser and denser until it, and matter nearby, collapse in on itself, producing enough heat to trigger nuclear fusion in its core, the source of most of the universe's energy now. The first stars were immense, eventually exploding as supernovas, forming many more, smaller stars. These coalesced, thanks to gravity, into galaxies.</p><p>One axiom of the Stelliferous era is that the bigger the star, the more quickly it burns through its energy, and then dies, typically in just a couple of million years. Smaller stars that consume energy more slowly stay active longer. In any event, stars — and galaxies — are coming and going all the time in this era, burning out and colliding.</p><p>Scientists predict that our Milky Way galaxy, for example, will crash into and combine with the neighboring Andromeda galaxy in about 4 billion years to form a new one astronomers are calling the Milkomeda galaxy.</p><p>Our solar system may actually survive that merger, amazingly, but don't get too complacent. About a billion years later, the Sun will start running out of hydrogen and begin enlarging into its red giant phase, eventually subsuming Earth and its companions, before shrining down to a white dwarf star.</p>
The Degenerate era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE1MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNTk3NDQyN30.gy4__ALBQrdbdm-byW5gQoaGNvFTuxP5KLYxEMBImNc/img.jpg?width=980" id="77f72" class="rm-shortcode" data-rm-shortcode-id="08bb56ea9fde2cee02d63ed472d79ca3" data-rm-shortcode-name="rebelmouse-image" />
Image source: Diego Barucco/Shutterstock/Big Think<p>Next up is the Degenerate era, which will begin about 1 quintillion years after the Big Bang, and last until 1 duodecillion after it. This is the period during which the remains of stars we see today will dominate the universe. Were we to look up — we'll assuredly be outta here long before then — we'd see a much darker sky with just a handful of dim pinpoints of light remaining: <a href="https://earthsky.org/space/evaporating-giant-exoplanet-white-dwarf-star" target="_blank">white dwarfs</a>, <a href="https://earthsky.org/space/new-observations-where-stars-end-and-brown-dwarfs-begin" target="_blank">brown dwarfs</a>, and <a href="https://earthsky.org/astronomy-essentials/definition-what-is-a-neutron-star" target="_blank">neutron stars</a>. These"degenerate stars" are much cooler and less light-emitting than what we see up there now. Occasionally, star corpses will pair off into orbital death spirals that result in a brief flash of energy as they collide, and their combined mass may become low-wattage stars that will last for a little while in cosmic-timescale terms. But mostly the skies will be be bereft of light in the visible spectrum.</p><p>During this era, small brown dwarfs will wind up holding most of the available hydrogen, and black holes will grow and grow and grow, fed on stellar remains. With so little hydrogen around for the formation of new stars, the universe will grow duller and duller, colder and colder.</p><p>And then the protons, having been around since the beginning of the universe will start dying off, dissolving matter, leaving behind a universe of subatomic particles, unclaimed radiation…and black holes.</p>
The Black Hole era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMjE0OTQ2MX0.ifwOQJgU0uItiSRg9z8IxFD9jmfXlfrw6Jc1y-22FuQ/img.jpg?width=980" id="103ea" class="rm-shortcode" data-rm-shortcode-id="f0e6a71dacf95ee780dd7a1eadde288d" data-rm-shortcode-name="rebelmouse-image" />
Image source: Vadim Sadovski/Shutterstock/Big Think<p> For a considerable length of time, black holes will dominate the universe, pulling in what mass and energy still remain. </p><p> Eventually, though, black holes evaporate, albeit super-slowly, leaking small bits of their contents as they do. Plait estimates that a small black hole 50 times the mass of the sun would take about 10<sup>68</sup> years to dissipate. A massive one? A 1 followed by 92 zeros. </p><p> When a black hole finally drips to its last drop, a small pop of light occurs letting out some of the only remaining energy in the universe. At that point, at 10<sup>92</sup>, the universe will be pretty much history, containing only low-energy, very weak subatomic particles and photons. </p>
The Dark Era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE5NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0Mzg5OTEyMH0.AwiPRGJlGIcQjjSoRLi6V3g5klRYtxQJIpHFgZdZkuo/img.jpg?width=980" id="60c77" class="rm-shortcode" data-rm-shortcode-id="7a857fb7f0d85cf4a248dbb3350a6e1c" data-rm-shortcode-name="rebelmouse-image" />
Image source: Big Think<p>We can sum this up pretty easily. Lights out. Forever.</p>
UNC School of Medicine researchers identified the amino acid responsible for the trip.
- Researchers at UNC's School of Medicine have discovered the protein responsible for LSD's psychedelic effects.
- A single amino acid—part of the protein, Gαq—activates the mind-bending experience.
- The researchers hope this identification helps shape depression treatment.
What is Bicycle Day?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="d346092205da3c9ed10bad283222c9f1"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/L32mAiLXnLs?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Back in the world of clinical science, LSD has always showed promise. That trend continues as restrictions are finally easing up. Understanding LSD's effects on our brain's complex system of networks is an important step toward discovering therapeutic actions. As Roth <a href="https://www.inverse.com/mind-body/how-lsd-binds-to-the-brain-study" target="_blank">says</a> of his research,</p><p style="margin-left: 20px;">"Now we know how psychedelic drugs work – finally! Now we can use this information to, hopefully, discover better medications for many psychiatric diseases."</p><p>Using X-ray crystallography, Roth's team discovered a single amino acid—a building block of the protein, Gαq—responsible for binding to serotonin receptors. As LSD is only a partial agonist, they also experimented with a full-agonist designer psychedelic in order to observe complete receptor activation. This amino acid appears to be the master switch for the psychedelic experience. </p><p>While psilocybin has been in the news, the psychedelic renaissance is expanding in all directions. Phase 1 clinical trials on the <a href="https://newatlas.com/science/landmark-clinical-trial-lsd-mdma-mindmed/" target="_blank">combination</a> of LSD, MDMA, and psychotherapy will soon commence. LSD's effects on <a href="https://clinicaltrials.gov/ct2/show/NCT03866252" target="_blank" rel="noopener noreferrer">Major Depressive Disorder</a> and <a href="https://www.sciencealert.com/first-clinical-trial-shows-micro-doses-of-lsd-can-increase-a-person-s-pain-tolerance" target="_blank">pain management</a> are ongoing. With the <a href="https://www.bloomberg.com/news/articles/2020-09-18/-magic-mushroom-company-moves-toward-mainstream-in-nasdaq-ipo" target="_blank" rel="noopener noreferrer">first psychedelics company</a> to IPO on the American stock market, along with hundreds of millions of dollars of investment flowing into similar companies and organizations, the push for legalized psychedelics intensifies. </p>
Credit: ynsga / Shutterstock<p>Researchers are actively attempting to remove the hallucinogenic component of psychedelics for widespread therapeutic usage—<a href="https://www.healtheuropa.eu/could-ibogaine-offer-a-revolutionary-long-term-solution-to-addiction/100635/" target="_blank">trials</a> using ibogaine for addiction treatment, for example. Identifying the chemical effects of psychedelics on our brains is an essential step in that process.</p><p>Of course, believing psychedelics <em>only</em> matters to brain chemistry is problematic as well. The rituals associated with their use are just as relevant. The "<a href="https://en.wikipedia.org/wiki/Set_and_setting" target="_blank">set and setting</a>" model espoused by Timothy Leary reminds us that biology isn't everything; environmental factors play just as important a role in mental health. </p><p>Isolating specific chemicals without understanding the impact of the drug <em>and</em> the environment overlooks the holistic nature of the psychedelic experience. For example, ketamine trials <a href="https://bigthink.com/surprising-science/ketamine-depression" target="_self">were rushed</a> and could potentially backfire; we can't afford to make that mistake again. </p><p>Still, understanding the pathways LSD utilizes is an important step forward. As Roth says, "Our ultimate goal is to see if we can discover medications which are effective, like psilocybin, for depression but do not have the intense psychedelic actions." In a world where more people are growing anxious and depressed by the day, every intervention should be explored.</p><p> --</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank" rel="noopener noreferrer">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
A team of researchers have discovered the brain rhythmic activity that can split us from reality.
- Researchers have identified the key rhythmic brain activity that triggers a bizarre experience called dissociation in which people can feel detached from their identity and environment.
- This phenomena is experienced by about 2 percent to 10 percent of the population. Nearly 3 out of 4 individuals who have experienced a traumatic event will slip into a dissociative state either during the event or sometime after.
- The findings implicate a specific protein in a certain set of cells as key to the feeling of dissociation, and it could lead to better-targeted therapies for conditions in which dissociation can occur.
What is dissociation?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="bd2f1f29418bd4805bf1282001dca814"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/XF2zeOdE5GY?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Dissociation is an experience commonly described as a feeling of sudden detachment from the individual's identity and environment, almost like an out-of-body experience. This mysterious phenomena is experienced by about 2 percent to 10 percent of the population.</p><p>"This state often manifests as the perception of being on the outside looking in at the cockpit of the plane that's your body or mind — and what you're seeing you just don't consider to be yourself," explained senior author Karl Deisseroth, MD, PhD, <a href="https://med.stanford.edu/news/all-news/2020/09/researchers-pinpoint-brain-circuitry-underlying-dissociation.html" target="_blank" rel="noopener noreferrer">in a Stanford Medicine news release</a>. Deisseroth is a professor of bioengineering and of psychiatry and behavioral sciences, as well as a Howard Hughes Medical Institute investigator.</p><p>Nearly three-quarters of individuals who have experienced a traumatic event will slip into a dissociative state either during the event or in the hours or even weeks that follow, according to Deisseroth. Most of the time, the dissociative experiences end on their own within a few weeks of the trauma. But the eerie experience can become chronic, such as in cases of post-traumatic stress disorder, and extremely disruptive in daily life. The state of dissociation can also occur in epilepsy and be invoked by certain drugs. </p><p>Until now, no one has known what exactly is going on inside the brain triggering and sustaining the feeling of dissociation — and so it has been a challenge to figure out how to stop it and develop effective treatments. </p>
New Research: The Molecular Underpinnings of Dissociation<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQyNjk3My9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNTQ3MTI1NX0._nJoxm1eDcTsHsy1Y27JxNl2uR5hlbEYDWYoQlO0EAU/img.jpg?width=1245&coordinates=0%2C121%2C0%2C121&height=700" id="26e86" class="rm-shortcode" data-rm-shortcode-id="1094af23e35a498a8a6b691f1d0cbfaf" data-rm-shortcode-name="rebelmouse-image" alt="neurons" />
Neurons from a mouse spinal cord
Credit: NICHD on Flickr<p>Last week, in a study published in <a href="https://www.nature.com/articles/s41586-020-2731-9" target="_blank">Nature</a><a href="https://www.nature.com/articles/s41586-020-2731-9">,</a> Deisseroth and his colleagues at Stanford University uncovered a localized brain rhythm and molecule that underlies this state.</p><p>"This study has identified brain circuitry that plays a role in a well-defined subjective experience," said Deisseroth. "Beyond its potential medical implications, it gets at the question, 'What is the self?' That's a big one in law and literature, and important even for our own introspections."</p><p>The authors' findings implicate a specific protein existing in a particular set of cells as key to the feeling of dissociation. </p><p>The research team first used a technique called widefield calcium imaging to record brain-wide neuronal activity in lab mice. They observed and analyzed changes in those brain rhythms after the animals had been administered a range of drugs that are known to cause dissociative states: ketamine, phencyclidine (PCP), and dizocilpine (MK801). At a certain dosage of ketamine, the mice behaved in a way that suggested that they were likely experiencing dissociation. For example, when the animals were placed on an uncomfortably warm surface, they reacted to it by flicking their paws. However, they signaled that they didn't care enough about the unpleasantness to do what they would typically do in such a situation, which is to lick their paws to cool them off. This suggested a dissociation from the surrounding environment.</p><p>The drug produced oscillations in neuronal activity in a region of the mices' brain called the retrosplenial cortex, an area essential for various cognitive functions such as navigation and episodic memory (a unique memory of a specific event). The oscillations occurred at about 1-3 hertz (three cycles per second). The authors then examined the active cells in more detail by using two-photon imaging for higher resolution. This revealed that the oscillations were occurring only in layer 5 of the retrosplenial cortex. Next, the researchers recorded neuronal activity across other regions of the brain. </p><p>"Normally, other parts of the cortex and subcortex are functionally connected to neuronal activity in the retrosplenial cortex," Ken Solt and Oluwaseun Akeju wrote in <a href="https://www.nature.com/articles/d41586-020-02505-z#ref-CR1" target="_blank">Nature</a>. "However, ketamine caused a disconnect, such that many of these brain regions no longer communicated with the retrosplenial cortex."</p><p>The scientists then used optogenetics, a method of manipulating living tissue with light to control neural function, to stimulate neurons in the mice's retrosplenial cortex. When the scientists did this at a 2-hertz rhythm, they were able to cause dissociative behavior in the animals analogous to the behavior caused by ketamine without using drugs. The experiments conducted by the team displayed how a particular type of protein, an ion channel, was essential to the generation of the hertz signal that caused the dissociative behavior in mice. Scientists are hopeful that this protein could be a potential treatment target in the future. </p>