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In 2021, a group of scientists led by researchers at the University of North Carolina at Chapel Hill, Weill Cornell Medicine and NewYork-Presbyterian reported that the Moderna mRNA vaccine and a protein-based vaccine candidate containing an adjuvant, a substance that enhances immune responses, elicited durable neutralizing antibody responses to SARS-CoV-2 during infancy in pre-clinical research.
Now a follow-up study by the same group, published in Science Translational Medicine, has found that the 2-dose vaccines still provide protection against lung disease in rhesus macaques one year after they had been vaccinated as infants.
The co-senior authors of the paper are Kristina De Paris, PhD, professor of microbiology and immunology at the UNC School of Medicine, Sallie Permar, MD, PhD, chair of the Department of Pediatrics at Weill Cornell Medicine, and Koen K.A. Van Rompay, DVM, PhD, leader of the Infectious Disease Unit at the California National Primate Research at the University of California, Davis. Co-first authors are Emma C. Milligan at the Children’s Research Institute in the UNC School of Medicine and Katherine Olstad at the California National Primate Research Center.
To evaluate SARS-CoV-2 infant vaccination, the researchers immunized two groups of eight infant rhesus macaques at the California National Primate Research Center at 2 months of age and again four weeks later. Each animal received one of two vaccine types: a preclinical version of the Moderna mRNA vaccine or a vaccine combining a protein developed by the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health with a potent adjuvant formulation. Consisting of 3M’s molecular adjuvant 3M-052 formulated in a squalene emulsion by the Access to Advanced Health Institute (AAHI), the adjuvant formulation stimulates immune responses by engaging receptors on immune cells.
“Following up on our SARS-CoV-2 infant rhesus macaque study, we gave the animals a high-dose challenge with a SARS-CoV-2 variant one year later to assess durability of vaccine-induced immune responses and their efficacy,” Dr. De Paris said. “We found that both vaccines protected against lung disease, despite the fact that the challenge SARS-CoV-2 variants acquired numerous mutations in their spike protein that differed from the vaccine immunogen.”
Overall, the adjuvanted protein vaccine candidate maintained higher levels of neutralizing antibodies and provided superior protection compared to the mRNA vaccine, Dr. De Paris said. These data imply that these vaccines are safe and highly effective when given to young infant macaques. Furthermore, the results inform the optimization and development of SARS-CoV-2 vaccines in a way that may reduce the need for frequent boosters and protect special populations that don’t have fully developed immune systems, such as young children.
“With COVID-19, young infants are one of the most vulnerable pediatric populations. This fall, we are seeing a sharp rise in hospitalizations due to respiratory virus disease in infants as the result of a confluence of SARS-CoV-2, flu, and RSV circulation,” said Dr. Permar, who is also the Nancy C. Paduano Professor in Pediatrics at Weill Cornell Medicine and pediatrician-in-chief at NewYork-Presbyterian Komansky Children’s Hospital. “We should take every opportunity to provide safe and effective vaccine immunity to our youngest patients, including considering COVID-19 vaccination earlier than the currently recommended 6 months of age.”
“This study emphasizes the need to get human infants immunized against SARS-CoV-2 as much as possible, as the benefits are clear and long-lasting. It also highlights the value of animal models in infectious disease research,” Dr. Van Rompay said. “The lessons we learned and the resources and tools that were developed in the current study will be very valuable for future pandemic preparedness, to more effectively combat outbreaks with novel coronaviruses or other respiratory viruses in pediatric populations.”
This research was funded through grants from the National Institutes of Health (P01AI117915-06S1), (U54 CA260543), (P510D11107), (UM1 AI068618-15: HVTN/HPTN, CoVPN), (P30AI050410: UNC Center for AIDS Research), and (P30 CA016086: UNC-LCCC Flow Cytometry Core Facility).
Other authors are Caitlin A. Williams, Michael Mallory, Patricia Cano, Kaitlyn A. Cross, Jennifer E. Munt, Carolina Garrido, Lisa Lindesmith, Jennifer Watanabe, Jodie L. Usachenko, Lincoln Hopkins, Ramya Immareddy, Yashavanth Shaan Lakshmanappa, Sonny R. Elizaldi, Jamin W. Roh, Rebecca L. Sammak, JoAnn L. Yee, Savannah Herbek, Trover Scobey, Dieter Miehlke, Genevieve Fouda, Guido Ferrari, Hongmei Gao, Xiaoying Shen, Pamela A. Kozlowski, David Montefiori, Michael Hudgens, Darin K. Edwards, Andrea Carfi, Kizzmekia S. Corbett, Barney S. Graham, Christopher B. Fox, Mark Tomai, Smita S. Iyer, Ralph Baric, Rachel Reader, and Dirk P. Dittmer.

When ambulance crews bring patients to hospital they are meant to be able to handover their patients to A&E staff within 15 minutes.But an analysis by the BBC shows by late November more than 11,000 ambulances were spending over an hour stuck in queues outside hospital every week.That is one in seven of all arrivals and the highest since records began in 2010.The BBC’s health editor Hugh Pym joined two members of South Central Ambulance on shift in Milton Keynes to see the problems this is causing first-hand.

An interdisciplinary team of scientists from Cologne, Heidelberg and Munich have discovered a new function of a well-known enzyme: The signal peptidase complex in the endoplasmic reticulum cleaves faulty membrane proteins to initiate their degradation. In our cells, the endoplasmic reticulum is responsible for producing and controlling proteins that get secreted from the cell. The signal peptidase complex cuts these polypeptide chains to remove signal peptides that allow proteins to reach the endoplasmic reticulum in the first place, so that the mature proteins can fulfil their specific functions.
A research team led by Matthias Feige, Professor for Cellular Protein Biochemistry at the Technical University of Munich (TUM), and Marius Lemberg, Professor for Biochemistry at the University of Cologne, has now discovered that the signal peptidase complex has a hitherto unknown function in another key process in cell biology: the quality control of membrane proteins. Their findings have now been published in Science under the title ‘The Human Signal Peptidase Complex Acts as a Quality Control Enzyme for Membrane Proteins.’
Each cell is surrounded by a lipid bilayer, which protects the interior of the cell, but also demands for regulated transport of molecules and signals across this insulating layer to enable a plethora of cellular functions. Membrane proteins are integrated into this lipid bilayer and perform these functions. They are essential for cell survival and serve as the most important drug targets. To function properly, membrane proteins need to adopt a well-defined three-dimensional structure at the atomic level. Failures in this process can result in faulty proteins, which in turn gives rise to numerous diseases, including cancer as well as metabolic and neurodegenerative disorders.
The team explored several disease-associated membrane proteins of our nervous system in order to better understand how our cells avoid that those faulty proteins damage them an and cause disease. During the course of their research, they observed that a protease — an enzyme that cleaves other proteins — initiates the degradation of the faulty mutant proteins. This degradation is essential to maintaining cellular function. However, they were unable to identify the protease involved. ‘All known candidates and commonly used inhibitors did not help us in our quest for the underlying molecular mechanism,’ said Feige.
The breakthrough came after the researchers identified potential cleavage sites for the signal peptidase complex. ‘According to established textbooks, the signal peptidase complex cleaves off signal peptides during the maturation of secretory proteins and so far, this was mostly believed to be its sole function,’ Lemberg added. However, the researchers identified the signal peptidase complex as the protease they were searching for, revealing that it plays an essential role in membrane protein quality control.
Subsequently, the interdisciplinary team of researchers identified several additional proteins that get cleaved and how this unexpected function might be regulated by the signal peptidase subunit SPCS1. ‘Since this factor is not essential for the initially described role in protein maturation, we realized that we were dealing with a previously unrecognized function,’ Feige explained.
‘Interestingly, SPCS1 is one of the only three genes that are down-regulated in all brain regions of Alzheimer’s disease patients, suggesting that our findings may have important implications for our understanding of human biology and age-associated disorders,’ Lemberg added. In Alzheimer’s disease, faulty proteins accumulate, which is thought to impair neuronal function. Feige concluded: ‘Our findings will help us to better understand how cells control the molecular shape of their proteins and lays the foundation for many future studies to come.’
The research was funded by the German Federal Ministry of Education and Research (BMBF), the German Science foundation (DFG), and the Fritz Thyssen Foundation.
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First discovered a year ago in South Africa, the SARS-CoV-2 variant later dubbed “Omicron” spread across the globe at incredible speed. It is still unclear exactly how, when and where this virus originated. Now, a study published in the journal Science by researchers from Charité – Universitätsmedizin Berlin and a network of African institutions shows that Omicron’s predecessors existed on the African continent long before cases were first identified, suggesting that Omicron emerged gradually over several months in different countries across Africa.
Since the beginning of the pandemic, the coronavirus has been constantly changing. The biggest leap seen in the evolution of SARS-CoV-2 to date was observed by researchers a year ago, when a variant was discovered that differed from the genome of the original virus by more than 50 mutations. First detected in a patient in South Africa in mid-November 2021, the variant later named Omicron BA.1 spread to 87 countries around the world within just a few weeks. By the end of December, it had replaced the previously dominant Delta variant worldwide.
Since then, speculations about the origin of this highly transmissible variant have centered around two main theories: Either the coronavirus jumped from a human to an animal where it evolved before infecting a human again as Omicron, or the virus survived in a person with a compromised immune system for a longer period of time and that’s where the mutations occurred. A new analysis of COVID-19 samples collected in Africa before the first detection of Omicron now casts doubt on both these hypotheses.
The analysis was carried out by an international research team led by Prof. Jan Felix Drexler, a scientist at the Institute of Virology at Charité and the German Center for Infection Research (DZIF). Other key partners in the European-African network included Stellenbosch University in South Africa and the Laboratory of Viral Hemorrhagic Fever (LFHB) in Benin. The scientists started by developing a special PCR test to specifically detect the Omicron variant BA.1. They then tested more than 13,000 respiratory samples from COVID-19 patients that had been taken in 22 African countries between mid-2021 and early 2022. In doing so, the research team found viruses with Omicron-specific mutations in 25 people from six different countries who contracted COVID-19 in August and September 2021 – two months before the variant was first detected in South Africa.
To learn more about Omicron’s origins, the researchers also decoded, or “sequenced,” the viral genome of some 670 samples. Such sequencing makes it possible to detect new mutations and identify novel viral lineages. The team discovered several viruses that showed varying degrees of similarity to Omicron, but they were not identical. “Our data show that Omicron had different ancestors that interacted with each other and circulated in Africa, sometimes concurrently, for months,” explains Prof. Drexler. “This suggests that the BA.1 Omicron variant evolved gradually, during which time the virus increasingly adapted to existing human immunity.” In addition, the PCR data led the researchers to conclude that although Omicron did not originate solely in South Africa, it first dominated infection rates there before spreading from south to north across the African continent within only a few weeks.
“This means Omicron’s sudden rise cannot be attributed to a jump from the animal kingdom or the emergence in a single immunocompromised person, although these two scenarios may have also played a role in the evolution of the virus,” says Prof. Drexler. “The fact that Omicron caught us by surprise is instead due to the diagnostic blind spot that exists in large parts of Africa, where presumably only a small fraction of SARS-CoV-2 infections are even recorded. Omicron’s gradual evolution was therefore simply overlooked. So it is important that we now significantly strengthen diagnostic surveillance systems on the African continent and in comparable regions of the Global South, while also facilitating global data sharing. Only good data can prevent policymakers from implementing potentially effective containment measures, such as travel restrictions, at the wrong time, which can end up causing more economic and social harm than good.”
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Ketamine, an established anesthetic and increasingly popular antidepressant, dramatically reorganizes activity in the brain, as if a switch had been flipped on its active circuits, according to a new study by Penn Medicine researchers. In a Nature Neuroscience paper released this month, the team described starkly changed neuronal activity patterns in the cerebral cortex of animal models after ketamine administration — observing normally active neurons that were silenced and another set that were normally quiet suddenly springing to action. This ketamine-induced activity switch in key brain regions tied to depression may impact our understanding of ketamine’s treatment effects and future research in the field of neuropsychiatry.
“Our surprising results reveal two distinct populations of cortical neurons, one engaged in normal awake brain function, the other linked to the ketamine-induced brain state,” said the co-lead and co-senior author Joseph Cichon, MD, PhD, an assistant professor of Anesthesiology and Critical Care and Neuroscience in the Perelman School of Medicine at the University of Pennsylvania. “It’s possible that this new network induced by ketamine enables dreams, hypnosis, or some type of unconscious state. And if that is determined to be true, this could also signal that it is the place where ketamine’s therapeutic effects take place.”
Anesthesiologists routinely deliver anesthetic drugs before surgeries to reversibly alter activity in the brain so that it enters its unconscious state. Since its synthesis in the 1960s, ketamine has been a mainstay in anesthesia practice because of its reliable physiological effects and safety profile. One of ketamine’s signature characteristics is that it maintains some activity states across the surface of the brain (the cortex). This contrasts with most anesthetics, which work by totally suppressing brain activity. It is these preserved neuronal activities that are thought to be important for ketamine’s antidepressant effects in key brain areas related to depression. But, to date, how ketamine exerts these clinical effects remains mysterious.
In their new study, the researchers analyzed mouse behaviors before and after they were administered ketamine, comparing them to control mice who received placebo saline. One key observation was that those given ketamine, within minutes of injection, exhibited behavioral changes consistent with what is seen in humans on the drug, including reduced mobility, impaired responses to sensory stimuli, which are collectively termed “dissociation.”
“We were hoping to pinpoint exactly what parts of the brain circuit ketamine affects when it’s administered so that we might open the door to better study of it and, down the road, more beneficial therapeutic use of it,” said co-lead and co-senior author Alex Proekt, MD, PhD, an associate professor of Anesthesiology and Critical Care at Penn.
Two-photon microscopy was used to image cortical brain tissue before and after ketamine treatment. By following individual neurons and their activity, they found that ketamine turned on silent cells and turned off previously active neurons.
The neuronal activity observed was traced to ketamine’s ability to block the activity of synaptic receptors — the junction between neurons — called NMDA receptors and ion channels called HCN channels. The researchers found that they could recreate ketamine’s effects without the medications by simply inhibiting these specific receptors and channels in the cortex. The scientists showed that ketamine weakens several sets of inhibitory cortical neurons that normally suppress other neurons. This allowed the normally quiet neurons, the ones usually being suppressed when ketamine wasn’t present, to become active.
The study showed that this dropout in inhibition was necessary for the activity switch in excitatory neurons — the neurons forming communication highways, and the main target of commonly prescribed antidepressant medications. More work will need to be undertaken to determine whether the ketamine-driven effects in excitatory and inhibitory neurons are the ones behind ketamine’s rapid antidepressant effects.
“While our study directly pertains to basic neuroscience, it does point at the greater potential of ketamine as a quick-acting antidepressant, among other applications,” said co-author Max Kelz, MD, PhD,a distinguished professor of Anesthesiology and vice chair of research in Anesthesiology and Critical Care. “Further research is needed to fully explore this, but the neuronal switch we found also underlies dissociated, hallucinatory states caused by some psychiatric illnesses.”
Support for the study was provided by the Foundation for Anesthesia Education and Research, and the National Institutes of Health (T32NS091006, R01GM124023-01A1, R01GM088156-08, R01 EY020765).

Scientists at Scripps Research have reported success in initial tests of a new, nanotech-based strategy against autoimmune diseases.
The scientists, who reported their results on November 23, 2022, in the journal ACS Nano, engineered cell-like “nanoparticles” that target only the immune cells driving an autoimmune reaction, leaving the rest of the immune system intact and healthy. The nanoparticles greatly delayed, and in some animals even prevented, severe disease in a mouse model of arthritis.
“The potential advantage of this approach is that it would enable safe, long-term treatment for autoimmune diseases where the immune system attacks its own tissues or organs — using a method that won’t cause broad immune suppression, as current treatments do,” says study senior author James Paulson, PhD, Cecil H. and Ida M. Green Chair of Chemistry in the Department of Molecular Medicine at Scripps Research.
Autoimmune diseases such as rheumatoid arthritis are caused when the immune system mistakenly attacks a person’s own tissues or organs. These illnesses affect an estimated 10 million people in the U.S. alone. Treatments are available and can be effective for many patients, but they tend to suppress the immune system indiscriminately, creating an enhanced susceptibility to infections and cancers — among other side effects.
Paulson and his team have taken an approach that targets the immune system more narrowly. Many autoimmune diseases are triggered or driven by immune attacks on just one protein in the patient’s body, known as a “self-antigen.” The idea underlying the nanoparticle strategy is to eliminate or deactivate only the immune cells that attack that self-antigen — an approach that could be at least as effective as broad immune suppression, without the side effects. Autoimmune diseases that are dominated by immune responses to a single self-antigen include some forms of arthritis, the skin blister disease known as pemphigus and the thyroid ailment Graves’ disease.
The researchers, including first author Katarzyna Brzezicka, PhD, a postdoctoral research associate in the Paulson lab, research assistant Britni Arlian, and other lab members, designed nanoparticles that could deactivate two types of immune cells: B cells and T cells. On its surface, each nanoparticle bore copies of a target self-antigen, plus a sugar-related molecule that can bind to a special “off switch” receptor on B cells called CD22. B cells, which make antibodies and are specific to different antigens, will effectively shut themselves off if they encounter both the particular antigen they target and the binding partner of CD22 at the same time.
Each nanoparticle also was laced with a powerful compound called rapamycin to stimulate the production of immune cells called regulatory T cells. Treg cells, as they’re also known, are responsible for suppressing other T cells needed to generate an autoimmune attack. The overall aim of the study was to effectively knock out only the B and T cells that recognize the self-antigen, leaving the rest of the B- and T-cell populations intact.
The researchers first demonstrated that their nanoparticle-based strategy could tolerize the mouse immune system to a chicken protein, ovalbumin, that would otherwise trigger a strong response. Next, they tested the strategy in a widely used mouse model of arthritis, in which the mouse immune system is genetically predisposed to attack a self-antigen called GPI. The scientists showed that treatment of the mice with GPI-tolerizing nanoparticles at the age of three weeks greatly delayed the development of arthritis signs that would normally appear a week or two later. In fact, about a third of the mice remained arthritis-free for the maximum follow-up period of 300 days. Tests confirmed that the treatment dramatically reduced the mice’s production of anti-GPI antibodies, and at the same time boosted their Treg populations.
Paulson says his team plans to follow up these highly promising results with further optimization of the nanoparticle strategy.
“We were able to ‘cure’ a third of these animals in this early demonstration, and I think there’s the potential to combine our nanoparticles with other immune modulator treatments to make it even more effective,” Paulson says. “So that will our next step — as well as demonstrating our technology against other autoimmune diseases caused by unwanted immune responses to a self-antigen.”
“Suppression of Autoimmune Rheumatoid Arthritis with Hybrid Nanoparticles That Induce B and T Cell Tolerance to Self-Antigen” was co-authored by Katarzyna Brzezicka, Britni Arlian, Shengyang Wang, Merissa Olmer, Martin Lotz, and James Paulson, all of Scripps Research.
This work was funded in part by the National Institutes of Health (R01AI050143, R01AI132790).

Engineering researchers have developed a battery-free, pill-shaped ingestible biosensing system designed to provide continuous monitoring in the intestinal environment. It gives scientists the ability to monitor gut metabolites in real time, which wasn’t possible before. This feat of technological integration could unlock new understanding of intestinal metabolite composition, which significantly impacts human health overall.
The work, led by engineers at the University of California San Diego, appears in the December issue of the journal Nature Communications.
The ingestible, biofuel-driven sensor facilitates in-situ access to the small intestine, making glucose monitoring easier while generating continuous results. These measurements provide a critical component of tracking overall gastrointestinal health, a major factor in studying nutrition, diagnosing and treating various diseases, preventing obesity, and more.
“In our experiments, the battery-free biosensor technology continuously monitored glucose levels in the small intestines of pigs 14 hours after ingestion, yielding measurements every five seconds for two to five hours,” said Ernesto De La Paz Andres, a nanoengineering graduate student at UC San Diego and one of the co-first authors on the paper. “Our next step is to reduce the size of the pills from the current 2.6 cm in length so they will be easier for human subjects to swallow.”
Older methods for directly monitoring the inside of the small intestine can cause significant discomfort for patients while generating only single short data recordings of an environment that continuously changes. By contrast, this biosensor provides access to continuous data readings over time. The platform could also be used to develop new ways to study the microbiome of the small intestine. The “smart pill” approach could lead to simpler and cheaper ways to monitor the small intestine, which could lead to significant cost savings in the future.
“Currently, the way to sample fluid inside the stomach and intestines is to do an endoscopy, where a catheter is inserted down your throat and into your GI tract by a doctor,” said Patrick Mercier, a professor of electrical and computer engineering at UC San Diego who led the team along with nanoengineering professor Joseph Wang. Wang and Mercier co-direct the UC San Diego Center for Wearable Sensors. “By combining the ultra-low-power circuit and wireless technologies from my lab with glucose-powered fuel cell and cutting-edge electrochemical sensing from the lab of UC San Diego nanoengineering professor Joseph Wang, we have an opportunity to create new modalities for understanding what is happening in the small intestine,” said Mercier.

mRNA COVID-19 vaccines are less effective against Omicron infections than other variants. A study publishing December 1 in the open access journal PLOS Medicine by Margaret L. Lind at the Yale School of Public Health, U.S. and colleagues suggests that the additional protection offered by the initial booster shot may be reduced among people with a previous COVID-19 infection.
Evidence indicates that primary (two-dose) and original booster mRNA (third dose) vaccination significantly reduces the risk of Omicron-related infection and severe outcomes in the general population. However, the benefit of mRNA COVID-19 vaccination in people who have previously experienced infection remains unclear.
In order to estimate the effectiveness of mRNA vaccination against Omicron infection among people with a prior documented infection, the researchers conducted a test-negative case control study using health records obtained through a COVID-19 study of vaccine-eligible people older than five who had at least one SARS-CoV-2 test in the Yale New Haven Health system electronic medical records.
The study group included 11,307 people who tested positive for SARS-CoV-2 between November 1, 2021 and April 30, 2022 as well as 130,041 control cases who tested negative in the same time period. The researchers then estimated vaccine effectiveness against infection and additionally whether an original booster dose was associated with increased protection beyond primary vaccination. This was achieved by comparing the odds of infection between boosted and booster-eligible people with and without a documented prior infection.
The researchers found that primary vaccination provided protection against Omicron infection among people with and without a documented prior infection. While original booster vaccination was associated with additional protection against Omicron infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection.
The researchers emphasize that while the initial booster may not provide additional benefits in preventing Omicron infection in some people, it still offers the best protection against severe illness and hospitalization, according to previous studies. This study was limited to Omicron infections and should be considered alongside other existing and future studies examining the relative benefits of booster doses against severe COVID-19 disease among people with and without prior infections. Additionally, this analysis was conducted prior to the distribution of the bivalent COVID-19 booster and the findings are limited to associations between the original vaccines and Omicron infection.
Lind adds, “In this retrospective study, we found that primary mRNA vaccination provides moderate protection against Omicron (BA.1 lineage) infection regardless of prior infection history. However, the relative benefits of an original booster dose against Omicron infection may be affected by a person’s history of prior SARS-CoV-2 infection.”
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Opioid-related overdose is now a leading cause of accidental death in the United States and Canada. A study published December 1st in the open access journal PLOS Medicine by Mary Clare Kennedy at University of British Columbia, Kelowna, Canada, and colleagues suggests discontinuing prescribed opioids was associated with increased overdose risk.
Canada and the United States have implemented guidelines to restrict opioid prescribing for chronic pain in an effort to reduce opioid-related illness and death. However, the effects of discontinuing opioid treatments on overdose risk are understudied. In order to better understand associations between discontinuation of prescribed opioid therapy for pain and risk of overdose, researchers conducted a retrospective cohort study of people receiving long-term opioid therapy for pain in British Columbia between October 2014 and June 2018. They analyzed the medical histories of 14,037 patients registered with the provincial health insurance client roster in British Columbia who had been on opioid therapy for at least 90 days.
The researchers found that discontinuing opioid therapy for pain was associated with increased overdose risk among people without opioid use disorder (OUD). Yet the association was stronger in those with OUD, including those not receiving opioid agonist therapy (AHR = 3.18; 95% CI = 1.87 — 5.40, p

Early life experiences can impact the activity of our genes much later on and even affect longevity, finds a new study in fruit flies led by UCL researchers.
In the study published in Nature Aging, the scientists report that gene expression ‘memory’ can persist across the lifespan, and may present a novel target for improving late-life health.
Lead author Dr Nazif Alic (UCL Institute of Healthy Ageing, UCL Biosciences) said: “Health in old age partially depends on what a person experienced in their youth or even in the womb. Here, we have identified one way in which this happens, as changes in gene expression in youth can form a ‘memory’ that impacts health more than half a lifetime later.”
The scientists were building on their previous research in which they found that fruit flies fed a high-sugar diet early in life lived shorter lives, even after their diets were improved in adulthood. Here, they uncover the mechanism likely explaining the finding.
In their previous study, the researchers found that a high-sugar diet inhibited a transcription factor called dFOXO, which is involved in glucose metabolism and is known from multiple studies to affect longevity, so they now sought to enact the opposite effect by directly increasing the activity of dFOXO. Transcription factors are proteins that regulate transcription, or copying, of information from DNA into messenger RNA, which is the first and key step in gene expression. For this study, the researchers activated dFOXO by increasing its levels in female fruit flies during the first three weeks of the fly’s adulthood.
They found that these early-life experiences caused changes to chromatin — a mixture of DNA and proteins that can be seen as the ‘packaging’ of DNA — that persisted and resulted in genes being expressed differently late in life. This counteracted some changes that would be expected as part of the normal ageing process, eventually improving health in late life and impacting the fruit flies’ lifespan more than a month (half a fruit fly lifetime) later.
The researchers say their findings could lead to ways to impact late-life health in people as well.
Dr Alic said: “What happens early on in an animal or person’s life can affect what their genes do late in life, for better or for worse. It may be that a poor diet early in life, for example, could impact our metabolism later in life by tweaking how our genes are expressed, even after substantial dietary changes over the years — but fortunately, it may well be possible to reverse this.
“Now that we know how gene expression memory can persist across the lifespan to affect gene activity, we may be able to develop ways to counteract these changes later in life to preserve health and enable people to stay healthy for longer.”
The study was supported by the Biotechnology and Biological Sciences Research Council and the Medical Research Council, and involved researchers from UCL, the University of Glasgow and Imperial College London.
Research at the UCL Institute of Healthy Ageing seeks to discover the biological mechanisms of ageing in order to understand causes of age-related diseases and improve human health at older ages, with recent studies identifying genes linked to longer human lifespan, and extending fruit fly lifespan by 48% with a combination drug treatment.
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