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“ An epigenetic biomarker of aging for lifespan and healthspan ” is a 2018 paper published in Aging. Its authors are Morgan Levine and collaborators, including Steve Horvath, the developer of the Horvath aging clock. The paper proposes a new biomarker of aging that enables prediction of several aging-related outcomes. Predicted outcomes include all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. This biomarker is known as the PhenoAge Clock, or the Levine Clock. Essentially, everyone has two ages. CNN explains that we have a chronological age, which is how old the calendar says you are. And we have a phenotypic or biological age, which is basically the age at which your body functions, compared to average fitness or health levels. "People of the same chronological age aren't all at the same risk for developing cardiovascular disease or cancer or even dying," said Levine as reported by CNN. "What [the biological age] does is actually give us a better idea of where someone stands for their age." "In my lab, we work on a lot of different types of aging measures," Levine continued. "One of the most recent ones is based on blood measures you get at your normal doctor's appointment. We basically take those and combine them using different algorithms to get what we call someone's phenotypic age or biological age." Levine and her team identified nine biomarkers taken in a simple blood test that seemed to be the most influential on lifespan, explains CNN. The biomarkers include blood sugar, kidney and liver measures, and immune and inflammatory measures. While PhenoAge was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. It is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important aspects of aging. Levine and her team found that increased PhenoAge “is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures.” A recent review article was published by the Simons Foundation. It notes that the Levine Clock, and other “second-generation” clocks, appear to better represent biological age than the first-generation clocks. These second-generation clocks may enable more informative studies that aim to understand aging in order to slow or prevent its effects. And this -- to slow down or prevent the effects of aging -- is the goal. "I think the most exciting thing about this research is that these things aren't set in stone," said Levine as reported by CNN. "We actually know a lot about how to change some of these markers.” By delaying the onset of diseases and physical and mental problems related to aging, "people can still be engaged in society," Levine concluded. "I think that is the ideal we should be striving for."

Pfizer announced that its COVID-19 oral antiviral candidate, Paxlovid, significantly reduced hospitalization and death. This was based on an interim analysis of the results of a clinical study of non-hospitalized adult patients with COVID-19, who were at high risk of progressing to severe illness. Paxlovid is specifically designed to be administered orally as a pill. So it can be prescribed at the first sign of infection or at first awareness of an exposure. This potentially helps patients avoid severe illness which can lead to hospitalization and death. Pfizer hopes to eventually offer the pill to people to take at home before they get sick enough to go to the hospital, CNN reports. It would be given in combination with an older antiviral drug called ritonavir. The company hopes to receive Emergency Use Authorization from the U.S. Food and Drug Administration as soon as possible. “Today’s news is a real game-changer in the global efforts to halt the devastation of this pandemic,” said Albert Bourla, CEO of Pfizer. “These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections, and eliminate up to nine out of ten hospitalizations.” The study evaluated data from 1219 adults. The participants had a laboratory-confirmed diagnosis of COVID-19 within a five-day period with mild to moderate symptoms. And they were required to have at least one characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19. The participants received Paxlovid or a placebo orally every 12 hours for five days. The results show an 89% reduction in risk of COVID-19-related hospitalization or death. 0.8% of the participants who received Paxlovid were hospitalized (with no deaths). This compares to 7% of the participants who received placebo and were hospitalized or died (with 7 deaths). “I think it's a great day for humanity,” said Bourla in conversation with CNN. Earlier this month, the UK medicines regulator approved Molnupiravir. It's a COVID antiviral developed by Merck and Ridgeback Therapeutics. This was reported in an article by biomedical technology professor Alexander Edwards, published in The Conversation. Among adults with mild to moderate COVID, who were at risk of developing serious disease, molnupiravir cut the chances of being hospitalised or dying in half. Edwards explains the difference: “Molnupiravir disrupts the replication of the virus. It mimics a building block of the virus’s genetic material, and so when the virus reproduces, gets incorporated into its RNA. This creates errors in its genetic code, and when enough of these build up, an “error catastrophe” stops the virus reproducing altogether… Paxlovid also stops viral replication, but in a different way. It works by binding to an enzyme - called a protease - to stop it from functioning. The coronavirus needs this enzyme to be functional in order to reproduce.” Edwards adds that Molnupiravir should be taken as soon as possible following testing positive (and within five days of symptoms starting). And Paxlovid appears to be beneficial when administered within three to five days of symptom onset.

Researchers at Hiroshima University have suggested a link between chemistry and life. And they've built a prebiotic chemical precursor of biology. "Chemical evolution was first proposed in the 1920s as the idea that life first originated with the formation of macromolecules from simple small molecules, and those macromolecules formed molecular assemblies that could proliferate," says researcher Muneyuki Matsuo in a press release issued by Hiroshima University. "However, the origin of molecular assemblies that proliferate from small molecules has remained a mystery for about a hundred years since the advent of the chemical evolution scenario. It has been the missing link between chemistry and biology in the origin of life." A paper is published in Nature Communications. It reports that the researchers designed and synthesized a small molecule derived from amino acids, as a precursor to the self-assembly of primitive cells. When added to room temperature water at atmospheric pressure, the amino acid derivatives condensed into droplets. And the droplets grew in size and in number when fed with more amino acids. "A droplet-based protocell could have served as a link between 'chemistry' and 'biology' during the origins of life," adds Matsuo. "This study may serve to explain the emergence of the first living organisms on primordial Earth… [Our] results suggest that droplets became evolvable molecular aggregates - one of which became our common ancestor." The researchers claim to have advanced toward solving “the long-standing mystery of how prebiotic ancestors were able to proliferate and survive by selectively concentrating prebiotic chemicals.” They plan to continue investigating the process of evolution from amino acid derivatives to primitive living cells. And they plan to improve their platform to verify and study the origins of life and continued evolution. The researchers also found that the droplets could concentrate nucleic acids (genetic material). And they were more likely to survive against external stimuli if they exhibited this function. To me, this is very interesting, because it seems to imply that lifeless chemistry exhibits a drive toward life. In fact, the authors say that they were inspired by the work of Nobel Prize winning biochemist Christian de Duve. And they cite de Duve’s book, “ Blueprint for a Cell: The Nature and Origin of Life.” Life, according to de Duve’s book, is an intrinsic part of the universe. “Wherever and whenever conditions are favorable, as they were here on Earth, and probably were, are, or will be elsewhere, the universe cannot but blossom into life.”

Epigenetic clocks, like the Horvath aging clock described in a previous post, capture aging processes at the molecular level. "It's well known that people age at different rates," said ophthalmologist and geneticist Kang Zhang in a 2012 press release issued by UC San Diego. "Some people in their 70s look like they're in their 50s, while others in their 50s look like they're in their 70s." The press release describes and comments upon the results of a study published in Molecular Cell. In the study, researchers led by Zhang and bioengineer Trey Ideker described biomarkers of aging and developed a model to quantify how aging occurs at the level of genes and molecules. This not only provides a more precise way to determine how old someone is, but could also permit doctors to anticipate or treat ailments and diseases that come with the passage of time. When we become older, a recent article published by the Simons Foundation explains, the activity of our genes becomes less tightly regulated than in our youth. This is due to a vast reshuffling of gene-regulating markers on our DNA. “This change involves small chemical tags known as DNA methylation marks, which are distributed by the millions throughout our genome and often silence gene expression. They are one form of the heritable changes, known as epigenetic modifications, that determine how cells use their genes.” The scientists led by Zhang and Ideker found that an individual's "methylome" (the entire set of human methylation markers and changes across a whole genome) predictably varies over time. And this provides a way to determine a person's actual biological age from just a blood sample. "It's the majority of the methylome that accurately predicts age, not just a few key genes," said Ideker. "The methylation state decays over time along the entire genome. You look in the body, into the cells, of young people and methylation occurs very distinctly in some spots and not in others. It's very structured. Over time, though, methylation sites get fuzzier; the boundaries blur." At the molecular level of the methylome, individual bodies age at varying rates. And even within the same body, different organs age differently. Moreover, cancer cells age differently than their surrounding normal cells. The findings have broad practical implications and “potentially huge medical import.” The researchers built a quantitative model of aging using data from hundreds of people all over the age spectrum. And they selected a set of 71 methylation markers that are highly predictive of age. This aging clock is often referred to as the Hannum epigenetic clock. Gregory Hannum, the first author of the study, is the researcher who found that the strong correlation with age overshadowed other associations in the data. “[Hannum] says, ‘Guys, I just can’t find any cancer signal. You know why? Because that damn age is such a pesky covariant. So many of the methylation marks just track age, and I can’t get rid of that signal,’” Ideker reported. “There was a pause, and we said, ‘You know, that’s interesting.’” The Horvath clock, based on a similar strategy, was developed soon after. Many studies have used the Hannum and Horvath clocks to establish links between accelerated epigenetic aging and conditions from heart disease and cancer to depression, Alzheimer’s disease, chronic pain, and cognitive functioning decline.

Researchers at University Miguel Hernández, Netherlands Institute of Neuroscience, and University of Utah (USA), have enabled a blind woman to see with a form of artificial vision based on a brain implant. This represents a leap forward for scientists hoping to create a visual brain prosthesis to increase independence of the blind. A long-held dream of scientists is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists. "This work is likely to become a milestone for the development of new technologies that could transform the treatment of blindness," said researcher P. Roelfsema. A study is published in Journal of Clinical Investigation. It describes how an array of penetrating electrodes produced a simple form of vision for a 58-year-old blind volunteer. "These results are very exciting because they demonstrate both safety and efficacy and could help to achieve a long-held dream of many scientists, which is the transfer information from the outside world directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight," said researcher Eduardo Fernández. The volunteer, a former science teacher, had been completely blind for 16 years at the time of the study. A microelectrode array composed of 100 microneedles was implanted into her visual cortex to both record from and stimulate neurons located close to the electrodes. She had no complications from the surgery, and researchers determined that the implant did not impair or negatively affect her brain function. "One goal of this research is to give a blind person more mobility," said researcher R. A. Normann. "It could allow them to identify a person, doorways, or cars. It could increase independence and safety. That's what we're working toward." The volunteer, who is a co-author of the paper, wore eyeglasses equipped with a miniature video camera. Specialized software encoded the visual data collected by the camera and sent it to the micro electrodes in the array located in her brain. The array then stimulated the surrounding neurons to produce white points of light known as “phosphenes” to create an image. With the help of the implant, the volunteer was able to identify lines, shapes, and simple letters evoked by different patterns of stimulation. Fernández cautioned that "although these preliminary results are very encouraging, we should be aware that there are still a number of important unanswered questions and that many problems have to be solved before a cortical visual prosthesis can be considered a viable clinical therapy." Future research tests will use a more sophisticated image encoder system. It will be capable of stimulating more electrodes simultaneously to elicit more complex visual images.

Aging researcher and geneticist Steve Horvath is a professor at UC Los Angeles. He's known for developing the Horvath aging clock. The clock is a highly accurate molecular biomarker of aging. A Nature commentary explains that “Horvath's clock emerges from epigenetics, the study of chemical and structural modifications made to the genome that do not alter the DNA sequence but that are passed along as cells divide and can influence how genes are expressed.” “I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types,” said Horvath in a 2013 paper published in Genome Biology. “I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.” A 2013 press release issued by UC Los Angeles explains that DNA methylation is a chemical modification of one of the four building blocks that make up our DNA. Horvath analyzed more than one hundred sets of data collected previously by researchers who had studied methylation in both healthy and cancerous human tissue, with thousands of samples of many types of tissue and cells taken from all over the body. Horvath charted how age affects DNA methylation levels from pre-birth through old age. His age predictor is based on hundreds of markers linked to methylation that change with age and are present throughout the body. Horvath tested the age predictor by comparing the biological age to the chronological age of tissues, and found that the age predictor is remarkably accurate. "It's surprising that one could develop a predictive tool that reliably keeps time across the human anatomy," said Horvath. "My approach really compared apples and oranges, or in this case, very different parts of the body - including brain, heart, lungs, liver, kidney and cartilage." An interesting application of the clock targets the detection of “age acceleration.” This acceleration reflects discrepancies between a person's epigenetic and chronological ages, either overall or in one particular part of their body. For example, healthy breast tissue “is about two to three years older than the rest of a woman's body," said Horvath. But if a woman has breast cancer, “the healthy tissue next to the tumor is an average of 12 years older than the rest of her body." Horvath’s best guess, as reported in the Nature commentary, is that the clock corresponds to the function of an epigenomic housekeeping system. The system helps to stabilize the genome by maintaining methylation patterns. The more active this mechanism, he proposes, the faster the epigenetic clock ticks. "The big question is whether the underlying biological clock controls a process that leads to aging," concluded Horvath. "If so, the clock will become an important biomarker for studying new therapeutic approaches to keeping us young." “The Horvath clock, a widely used biomarker of ageing, is one of a series of discoveries over the past two decades that are invigorating the science of life extension,” notes a recent Financial Times piece titled “Can we defeat death?”

Researchers at Florida State University have found a link between an individual's sense of purpose and their ability to recall vivid details. The researchers found that while both a sense of purpose and cognitive function made personal memories easier to recall, only a sense of purpose bestowed the benefits of vividness and coherence. "Personal memories serve really important functions in everyday life," says researcher Angelina Sutin in a press release issued by Florida State University. "They help us to set goals, control emotions and build intimacy with others.” “We also know people with a greater sense of purpose perform better on objective memory tests, like remembering a list of words,” added Sutin. "We were interested in whether purpose was also associated with the quality of memories of important personal experiences because such qualities may be one reason why purpose is associated with better mental and physical health." The researchers performed a study with hundreds of participants. First, the participants reported on their sense of purpose and completed tasks that measured their cognitive processing speed in January and February 2020. Then, in July 2020, the researchers measured and analyzed the ability of the participants to retrieve and describe recent personal memories about the Covid-19 pandemic. In a paper published in Memory, the researchers report that the participants with a stronger sense of purpose in life reported that their memories were more accessible, coherent, and vivid than participants with less purpose. "Memories help people to sustain their well-being, social connections and cognitive health," said researcher Antonio Terracciano. "This research gives us more insight into the connections between a sense of purpose and the richness of personal memories. The vividness of those memories and how they fit into a coherent narrative may be one pathway through which purpose leads to these better outcomes." Purpose in life has been consistently associated with better episodic memory. This research also shows a correlation between purpose and the richness of personal memory. According to the researchers, the results of the study suggest that individuals with a higher sense of purpose in life have “autobiographical memories with richer phenomenology.” Previous research has found numerous other benefits connected with having a sense of purpose, from a lower risk of death to better physical and mental health. The connection between life purpose and memory is not, the results of this study suggest, entirely due to the fewer depressive symptoms among individuals with a higher sense of purpose. Of course, having fewer depressive symptoms is an important mental health benefit in itself. This is, I think, very important advice for everyone’s health and well-being. Cultivate your sense of purpose. Find more and more good reasons to get out of bed in the morning. Care about something bigger than you. Do something good. And your physical and mental health may improve as a result.

Physicians and scientists at Beth Israel Deaconess Medical Center have developed a 12-week mind-body program. It takes a new approach to chronic back pain, which is the leading cause of disability worldwide. The experimental mind-body program is called “Psychophysiologic Symptom Relief Therapy” (PSRT). It is designed to address underlying stress factors and emotional issues related to chronic back pain. The last few weeks of the program focus on mindfulness-based stress reduction to provide the tools to better process current and future stress factors. "The current paradigm of pain management focuses mostly on treatment of a physical origin of pain, however, in many cases of chronic back pain a physical source of pain cannot be identified," says physician Michael W. Donnino in a press release issued by Beth Israel Deaconess Medical Center. "Our group focused on the hypothesis that non-specific back pain is the symptomatic manifestation of a psychological process, substantively driven by stress, repressed emotions and other psychological processes. The exact mechanism remains unclear, but an analogy could be made to other known effects of acute emotional states on acute physiological changes, such as how the emotion of embarrassment may result in the capillary vasodilation we know as blushing." A study is published in PAIN Reports. It reports that PSRT was highly beneficial for treating back pain when compared to standard care. 64% of research volunteers reported being 100% pain free six months later. 35 participants 18 to 67 years old, with chronic back pain that lacked a clear physical origin, participated in the study. The difference between the participants treated with PSRT and the other patients was apparent, added Donnino. "When patients recognize the relationship between the mind and their physical pain, this orientation sheds new light and provides them a basis to engage with the multifaceted program that works interchangeably to improve pain and disability.” The results of the study add to a growing body of evidence that psychological factors may be associated with at least some forms of chronic back pain. A related study was published in Electronics earlier this year. In it, Japanese researchers suggested that low back pain in the elderly is the result of poor “ proprioception,” or the body's ability to perceive its own position in space. An illustration of proprioception is given by the fact that you are (probably) able to touch the tip of your nose with your eyes closed, starting from any position and without any effort. This is proprioception at work. Poor proprioception in older people is caused, the researchers suggested, by a deterioration of sensory receptors called proprioceptors. The researchers demonstrated the possibility to manage low back pain by diagnosing and activating impaired proprioceptors with localized vibratory stimulations. I am one of the millions of sufferers from chronic back pain. I consider this as one of the many unpleasant things that just happen, inevitably, when you are not 20 anymore. And I have learned to ignore the chronic pain and just go on with life. I found that swimming and yoga help. And that is good enough for me. But I guess the Japanese researchers must be right. Bad posture is not only a result of chronic back pain but often a cause. That, in turn, may be caused by age-related degradation of body awareness that could be managed by medicine.

Researchers have suggested that Omega 3 supplements may reduce exercise-induced muscle damage. This is due to the anti-inflammatory properties of Omega 3. Exercise-induced muscle damage results in transient muscle inflammation, strength loss, muscle soreness. These results may cause subsequent exercise avoidance. Symptoms of exercise-induced muscle damage include pain, swelling, muscle strength and power loss, reduced range of motion, delayed onset muscle soreness, and impaired recovery. These symptoms may result in overall impairment of exercise performance. Exercise-induced muscle damage is associated with inflammatory responses involving interleukin, acute phase proteins, and muscle specific creatine kinase. The researchers investigated the effects of Omega 3 supplements on exercise-induced muscle damage. And they reported the methods and results of the study in a paper published in Journal of the International Society of Sports Nutrition. Fourteen healthy, physically-active males participated in this experimental study. Exclusion criteria included age (outside 18-35 age range), smoking, gender, taking any medication (e.g. non-steroidal anti-inflammatory drugs), consuming fish oil supplements in the six months before the study, and the presence of any known immune, cardiovascular, or metabolic disease. On repeated visits to the laboratory, the participants performed exercises relevant to assessing exercise-induced muscle damage. The exercises included, for example, running downhill with a 10% slope. Perceived muscle soreness and various indicators relevant to exercise-induced muscle damage were evaluated and measured before and immediately after exercise. The participants were divided in two groups following standard trial practices. One group received placebo. Participants in the other group received Omega 3 supplements. The supplements consisted of three gelcaps per day. Participants consumed one in the morning, one at lunch, and one in the evening. Each gelcap contained 1040 mg of Omega 3 polyunsaturated fatty acids. The results of the study indicate that muscle soreness was significantly lower in the Omega 3 group, compared to the placebo group, one day after the test. No significant difference in peak power output was observed between groups. The researchers conclude that Omega 3 supplements for four weeks may successfully attenuate exercise-induced muscle damage. While improvements in exercise performance were not detected, the researchers are persuaded that these findings have relevance to soreness-associated exercise avoidance. Strategies to reduce muscle damage and inflammation following exercise-induced muscle damage can be of use to individuals interested in increasing their rate of recovery and maintaining performance. Thrivous develops Omega Cardioprotector to enhance heart and circulation function for better aging. Each serving of Omega provides a clinical dose of Omega 3 Lysine Complex, which has no fishy smell or taste, and is five times more bioavailable than traditional Omega 3 gelcaps. Reflecting this study, Omega may also enhance exercise recovery. Get your Omega in the Thrivous store today!

Researchers led by Rutgers University have found that learning - a universal feature of intelligence in living beings - can be mimicked in solid state matter. This is a discovery that could inspire new algorithms for Artificial Intelligence (AI). And that may enable advances in human enhancement. A research paper is published in PNAS. It indicates that materials with highly tunable electronic structures, and a dynamic response to environmental stimuli, could be particularly suited for neuromorphic devices. Such devices work like the human brain. The researchers studied how the electrical conductivity of nickel oxide, a special type of insulating material, responded when its environment was changed repeatedly over various time intervals. Nickel oxide is a Mott insulator with properties that are strongly dependent on quantum effects. And it can become a conductor in appropriate conditions. "The goal was to find a material whose electrical conductivity can be tuned by modulating the concentration of atomic defects with external stimuli such as oxygen, ozone and light," says researcher Subhasish Mandal in a press release issued by Rutgers University. "We studied how this material behaves when we dope the system with oxygen or hydrogen, and most importantly, how the external stimulation changes the material's electronic properties." Habituation and sensitization, defined respectively as ignoring frequent stimuli and overreacting to a stimulus in presence of another, are fundamental forms of learning and adaptation in biological organisms. In the PNAS paper, the researchers demonstrate these universal learning characteristics in an inorganic system of binary nickel oxide under different environmental stimuli. Electronic plasticity is maintained by driving the system out of equilibrium and modulating defect concentration in dynamic environments. "The most interesting part of our results is that it demonstrates universal learning characteristics such as habituation and sensitization that we generally find in living species," adds Mandal. "These material characteristics in turn can inspire new algorithms for artificial intelligence. Much as collective motion of birds or fish have inspired AI, we believe collective behavior of electrons in a quantum solid can do the same in the future.” I think this is an important result because it shows that the biological brain is but one of a wider class of physical systems that can learn. If a quantum cloud of electrons in a solid can learn how to solve problems for AI applications, it could also provide a model for human learning and thinking. Besides machine learning and AI, it seems plausible to me that learning matter could be used in next-generation brain interfaces and implants, able to interface with biological neurons better than today’s electronics. "The growing field of AI requires hardware that can host adaptive memory properties beyond what is used in today's computers," concludes Mandal. "We find that nickel oxide insulators, which historically have been restricted to academic pursuits, might be interesting candidates to be tested in future for brain-inspired computers and robotics."