A new genetic analysis using data from over five million people has provided a clearer understanding of the risk of going on to live with obesity. New research led by the Universities of Copenhagen and Bristol shows analyzing genes at a young age may support early strategies to prevent obesity developing later in life.

The World Obesity Federation expects more than half the global population to become overweight or obese by 2035. However, treatment strategies such as lifestyle change, surgery and medications are not universally available or effective.

By drawing on genetic data from over five million people, an international team of researchers, have created a measure called a polygenic risk score (PGS) that is reliably associated with adulthood obesity and shows consistent and indicative patterns in early childhood. The findings could help to identify children and adolescents at higher genetic risk of developing obesity in later life, who could benefit from targeted preventative strategies, such as lifestyle interventions, at a younger age.

"What makes the score so powerful is the consistency of associations between the genetic score and body mass index before the age of five and through to adulthood - timing that starts well before other risk factors start to shape their weight later in childhood. Intervening at this point could theoretically make a huge impact," said Assistant Professor Roelof Smit at the University of Copenhagen and lead author of the research published in the journal Nature Medicine.

Twice as effective at predicting obesity as the next best method

The subtle variations in people's genomes can have a real impact on health when acting together. Thousands of genetic variants have been identified that increase the risk of obesity, for example, variants that act in the brain and influence appetite. A PGS is like a calculator that combines the effects of the different risk variants that a person carries and provides an overall score. The PGS was able to explain almost a fifth (17%) of a person's variation in body mass index - much higher than in previous studies.

To create these PGS, the scientists drew on the genetic data of more than five million people - the largest and most diverse genetic dataset ever - including genetic data from the Genetic Investigation of ANthropometric Traits (GIANT) consortium and consumer DNA testing firm, 23andMe. The researchers then tested whether their new PGS was associated with obesity using datasets of the physical and genetic characteristics of more than 500,000 people, including BMI data tracked over time from the Children of the 90s study. They found that their new PGS was twice as effective as the previous best method at predicting a person's risk of developing obesity.

Dr Kaitlin Wade, Associate Professor in Epidemiology at the University of Bristol and second author on this paper said: "Obesity is a major public health issue, with many factors contributing to its development, including genetics, environment, lifestyle and behaviour. These factors likely vary across a person's life, and we believe that some of these originate in childhood.

"We were delighted to contribute data from the Children of the 90s study to this exceptional and insightful research into the genetic architecture of obesity. We hope this work will contribute to detecting individuals at high risk of developing obesity at an earlier age, which could have a vast clinical and public health impact in the future."

Genetics is not destiny

The research team also investigated the relationship between a person's genetic risk of obesity and the impact of lifestyle weight loss interventions, such as diet and exercise. They discovered that people with a higher genetic risk of obesity were more responsive to interventions but also regained weight more quickly when the interventions ended.

Despite drawing on the genomes of a wider population, the new PGS has its limitations. For example, it was far better at predicting obesity in people with European-like ancestry than in people with African ancestry. This flags the need for work like this in more representative groups.

Read more …New genetic test predicts obesity before you start kindergarten

As revenues from the anti-aging market -- riddled with hope and thousands of supplements-- surged past $500 million last year, Emory University researchers identified a compound that actively delays aging in cells and organisms.

A newly published study in Nature Partner Journals' Aging demonstrates that psilocin, a byproduct of consuming psilocybin, the active ingredient in psychedelic mushrooms, extended the cellular lifespan of human skin and lung cells by more than 50%.

In parallel, researchers also conducted the first long-term in vivo study evaluating the systemic effects of psilocybin in aged mice of 19 months, or the equivalent of 60-65 human years. Results indicated that the mice that received an initial low dose of psilocybin of 5 mg, followed by a monthly high dose of 15 mg for 10 months, had a 30% increase in survival compared to mice that did not receive any. These mice also displayed healthier physical features, such as improved fur quality, fewer white hairs and hair regrowth.

While traditionally researched for its mental health benefits, this study suggests that psilocybin impacts multiple hallmarks of aging by reducing oxidative stress, improving DNA repair responses, and preserving telomere length. Telomeres are the structured ends of a chromosome, protecting it from damage that could lead to the formation of age-related diseases, such as cancer, neurodegeneration, or cardiovascular disease. These foundational processes influence human aging and the onset of these chronic diseases.

The study concludes that psilocybin may have the potential to revolutionize anti-aging therapies and could be an impactful intervention in an aging population.

"Most cells in the body express serotonin receptors, and this study opens a new frontier for how psilocybin could influence systemic aging processes, particularly when administered later in life," says Louise Hecker, PhD, senior author on the study, and former associate professor at Emory University, where the research was initiated and funded.

While much of what researchers know about psilocybin relates to the brain, few studies have examined its systemic impacts. Many people associate psilocybin with the hallucinogenic impacts, but the majority of the cells in the body express serotonin receptors.

"Our study opens new questions about what long-term treatments can do. Additionally, even when the intervention is initiated late in life in mice, it still leads to improved survival,which is clinically relevant in healthy aging," adds Hecker, currently an associate professor at Baylor College of Medicine.

This news comes on the heels of KFF's recent report that U.S. life expectancy is still below that of other countries similar in income and size, with an average lifespan of 78.4 years, compared to 82.5 years elsewhere. Not only was it the lowest, but as the lifespan in similar countries increased by 7.9 years from 1980-2022, whereas the U.S. life expectancy has only increased by 4.7 years.

"This study provides strong preclinical evidence that psilocybin may contribute to healthier aging -- not just a longer lifespan, but a better quality of life in later years," says Director of Psychedelic Research at Emory University's Department of Psychiatry Ali John Zarrabi, MD. "As a palliative care physician-scientist, one of my biggest concerns is prolonging life at the cost of dignity and function. But these mice weren't just surviving longer -- they experienced better aging," adds Zarrabi, co-investigator of the study.

Zarrabi emphasized the importance of further research in older adults, as well as the well-documented overlap between physical and mental health.

"Emory is actively involved in Phase II and III clinical trials of psilocybin-assisted therapy for depression, and these results suggest we also need to understand psilocybin's systemic effects in aging populations," says Zarrabi. "My hope is also that if psilocybin-assisted therapy is approved as an intervention for depression by the FDA in 2027, then having a better quality of life would also translate into a longer, healthier life."

The study was initiated at Emory University and funded by several awards, including the Imagine, Innovative, and Impact (I3) Award, Emory University School of Medicine; the Georgia CTSA NIH Award; and a grant from Emory's Woodruff Health Sciences Center for Health in Aging.

Read more …Magic mushrooms rewind aging in mice—could they do the same for humans?

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