A panel of advisers to the Food and Drug Administration gave its endorsement Thursday to a seasonal mRNA flu vaccine that was developed by Moderna and that earlier this year became the subject of controversy when a top agency official briefly refused to even consider accepting it for review.

The Vaccines and Related Biological Products Advisory Committee — known as VRBPAC — voted unanimously that the benefits of the vaccine outweigh the risks for both adults aged 50 to 64, and those 65 and older. It remains to be seen what the FDA will decide, but staff presentations during the meeting suggested the agency sees the vaccine as having cleared sufficient hurdles to be licensed via a traditional pathway for the younger group, and an accelerated pathway for the older group. 

Multiple flu vaccines currently on the market were first licensed using an accelerated pathway, Wellington Sun, a former FDA employee, noted during the meeting’s public comment period. (After leaving FDA, Sun worked for Moderna, but he is no longer with the company.)

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Research headed by scientists at Arizona State University and Vanderbilt University suggest that experiences we face early in life may leave their marks on our health in ways that echo across decades, and even across the entire body.

The team’s study involves a unique group of free-living rhesus macaques who have been followed their entire lives to document their experiences. Pairing the animals’ histories with genomic data from 12 tissues collected in adulthood, the study has generated some of the clearest molecular evidence yet that early life adversity (ELA) leaves a lasting, system-wide impression at the epigenome, the biological layer on top of the human genome that regulates gene activity.

The team examined DNA methylation (DNAm) patterns, which can represent telltale aging hallmarks of the epigenome. DNA methylation is one of the most well-studied markers of aging and can be used to build “epigenetic clocks” that estimate both an organism’s chronological age—how long it has been alive—and biological age, which is how old it appears physiologically. Through their newly reported study, the researchers developed highly precise tissue-specific clocks, capable of predicting age within about one year of an individual’s chronological age.

Their findings challenge a common assumption that early adversity uniformly accelerates biological aging. Instead, the results suggest a more nuanced model, in which early experiences alter the trajectory of molecular aging, amplifying the effects of aging in some tissues, such as the pituitary, but not others. These findings further suggest that the well-documented effects of early adversity on health operate, at least in part, through mechanisms that are not directly linked to aging.

“Our goal was to understand how aging unfolds across the body, and how early experiences might influence that process,” said Noah Snyder-Mackler, PhD, a professor in Arizona State University’s School of Life Sciences. “What we found is that early life adversity leaves a coordinated epigenetic signature that spans multiple tissues—but it doesn’t simply accelerate aging in a uniform way.”

Snyder-Mackler is co-senior author of the team’s published paper in Science, titled “Age and early life adversity shape heterogeneity of the epigenome across tissues in macaques.” In their research article summary the team concluded “By generating multi-tissue DNAm data across the life course in animals with known social histories, we reveal a fundamental contrast in epigenomic remodeling: Age-associated epigenetic variations are highly tissue dependent, whereas the molecular effect of ELA represents a more coordinated, organism-wide response.”

Aging is universal, the authors wrote, but the pace of decline varies significantly both between and within individuals. “Identifying early patterns and biomarkers of aging—before overt pathophysiology—could enable earlier clinical intervention, and refining how patterns are linked between organs may clarify which aging hallmarks are shared across tissues versus which must be assayed in specific organs to predict disease.”

ELA has been linked to age-related diseases and reduced lifespan in both humans and other social animals. However, the team noted, “… we still know little about how early life exposures shape the biological mechanisms of aging across tissues, especially at the molecular level.” This is difficult to study in humans, because detailed life course information in combination with multi-tissue molecular data is very rare.

For their reported research the team studied 237 macaques, who live in semi-natural conditions on Cayo Santiago (colloquially referred to as “Monkey Island”), a 38-acre island off Puerto Rico’s east coast. The island is inhabited by over 1,500 free-ranging rhesus macaques and managed by the University of Puerto Rico and Caribbean Primate Research Center. By integrating multi-tissue DNA methylation collected in adulthood with detailed records of early life experiences, the team uncovered how adversity and aging interacted to shape biology at the molecular level.

“We focused on DNAm, an epigenetic modification that is one of the most studied hallmarks of aging,” the authors wrote. “… DNAm can be used for estimating ‘biological’ age using ‘epigenetic clocks,’ a measure linked to disease and mortality.” The team generated a dataset integrating multi-tissue DNAm profiles with extensive data on social and environmental conditions during the animals’ development, creating the opportunity to examine how age and early life adversity affect DNAm across the body.

What they found was that despite the epigenetic precision, aging did not occur uniformly across the body. Instead, the researchers found that age-related changes in DNA methylation were highly tissue dependent. Yet even amid this diversity, individuals showed a degree of internal consistency. Animals that appeared “biologically older” in one tissue tended to appear older in other tissues as well, suggesting that aging operates as a partially coordinated process across the body.

“Age-associated DNAm was predominantly tissue dependent, yet tissue-specific epigenetic clocks showed that epigenetic aging was relatively consistent within individuals,” the investigators stated. Co-senior author Amanda Lea, PhD, assistant professor of biological sciences at Vanderbilt University, added, “At a molecular level, aging looks very different depending on which tissue you examine,” said. “Blood, which is most commonly measured in human studies, only captures part of the picture.” Some tissues, like the thymus and pituitary gland, showed particularly strong and distinct age-related patterns, while others exhibited more subtle changes.

The study’s most novel insights came from examining early life adversity—defined through naturally occurring conditions such as maternal loss, low maternal social status, or growing up in a crowded social group. These experiences were not only associated with changes in DNA methylation, but in a strikingly coordinated way across tissues. “We found that each type of adversity tends to affect specific regions of the genome,” said Lea. “But once it targets those regions, the effects are often shared across multiple tissues.”

In total, the team identified thousands of genomic regions where DNA methylation was associated with early life adversity. These regions frequently overlapped with those affected by aging—but importantly, the direction of the effects was not consistent. “In some cases, adversity-related changes looked like accelerated aging. In others, they went in the opposite direction,” explained co-lead author Rachel Petersen, PhD, a Vanderbilt postdoctoral researcher. “This tells us that early adversity doesn’t simply ‘speed up’ aging.

“Instead, it reshapes the epigenome in more complex ways.” In their paper the researchers note, “Although ELA targeted many of the same loci as age, the directions of effects differed, which indicates that ELA does not uniformly increase epigenetic age.” Instead, they continued, “… ELA leaves a coordinated, cross-tissue epigenetic signature that is distinct from—yet intertwined with—age-related differences, which advances our understanding of how early environments sculpt the molecular foundations of aging and disease.”

The study also highlights the importance of studying multiple tissues. Many previous studies have relied on blood samples, which are relatively easy to collect. However, the new findings show that this approach may miss critical aspects of how aging and environmental exposures affect the body. “Different tissues have their own epigenetic landscapes and respond differently to both age and adversity,” said co-lead author Baptiste Sadoughi, DVM, an ASU postdoctoral researcher. “To fully understand health and disease, we need to take a whole-body perspective.”

The use of rhesus macaques, which share many biological and social similarities with humans, adds to the study’s relevance. Unlike laboratory animals, these macaques live in complex social environments, allowing researchers to capture naturally occurring variation in life experiences. “This kind of dataset is incredibly rare,” said Lea. “It allows us to connect detailed life histories with molecular changes across the body in a way that simply isn’t possible in most human studies.” In their research article summary the team noted that their collective findings “…  advance our understanding of how early environments sculpt the molecular foundations of aging and establish this comprehensive tissue atlas as a valuable resource for the scientific community.”

Beyond its scientific contributions, the research has important implications for understanding the developmental origins of health and disease. By showing how early experiences shape the epigenome across tissues, it provides a potential mechanism linking childhood conditions to later-life outcomes. “Early life is a critical window for biological development,” said Snyder-Mackler. “Our findings suggest that experiences during this period can leave lasting marks on the genome that influence health trajectories over the lifespan.”

At the same time, the complexity of the results offers a note of caution. Because all types of adversity do not have uniform effects, predicting long-term consequences will require a more detailed understanding of context, timing, and individual variation. “This is not a simple story,” Lea said. “But that’s what makes it exciting. We’re beginning to see how life experiences are written into our biology—and why those signatures might vary within and between individuals.” As researchers continue to explore the interplay between environment, epigenetics and aging, studies like this one are helping to redefine what it means to grow older—not just as a function of time, but as a dynamic process shaped by the unique experiences that can truly define our lives.

The post Impact of Early Life Adversity on Epigenome at Molecular Level Mapped in Macaques appeared first on GEN – Genetic Engineering and Biotechnology News.

DAKAR, Senegal — The Ebola outbreak in Congo and Uganda has claimed more than 200 lives in its first month and is the worst known outbreak at this stage, with up to 35,000 suspected potential contacts, Africa’s Centres for Disease Control and Prevention said on Thursday.

With 894 confirmed cases so far, the current outbreak is three times worse than a previous outbreak in Uganda in 2000, which had 281 cases at the same point, said Dr. Wessam Mankoula, a medical epidemiologist at Africa CDC.

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