In a groundbreaking study led by Daniela Jopp, Professor at the University of Lausanne (UNIL), researchers have uncovered intriguing insights into the secrets of longevity through an interdisciplinary project known as “SWISS100.” This initiative combines sociology, psychology, medicine, and biology to explore the factors contributing to the remarkable lifespan of Swiss centenarians. The biological component, spearheaded by Karl-Heinz Krause, Professor Emeritus at the University of Geneva’s Faculty of Medicine, delves into the molecular characteristics of individuals aged 100 and above.
Krause’s team conducted a comparative analysis involving 39 centenarians, 59 octogenarians, and 40 younger volunteers aged 30 to 60. “The octogenarians allow a more fine-grained analysis of how certain blood markers evolve over a lifetime, and help to distinguish normal ageing from the exceptional ageing of centenarians,” explains Krause. This study has revealed that oxidative stress levels are significantly lower in centenarians, offering a potential clue to their extended lifespans.
Key Findings: Oxidative Stress and Protein Profiles
The researchers measured 724 proteins in blood serum, focusing on 358 inflammatory markers and 366 cardiovascular markers, both critical areas for longevity. “Of these 724 proteins, 37 produced a truly remarkable result,” highlights Flavien Delhaes, a researcher at the Department of Cell Physiology and Metabolism at the University of Geneva and the study’s first author.
“In our centenarians, the profiles of these 37 proteins are closer to those of the youngest group than to those of octogenarians. This represents approximately 5% of the proteins measured, suggesting that centenarians do not entirely escape ageing, but that certain key mechanisms are significantly slowed down.”
The study identified five proteins linked to oxidative stress, suspected of accelerating ageing. Oxidative stress, primarily caused by free radicals, originates from chronic inflammation and dysfunctional mitochondria. “Do centenarians produce fewer free radicals, or do they have a more powerful antioxidant defence?” asks Krause. “The answer is very clear: centenarians have significantly lower levels of antioxidant proteins than the standard geriatric population. At first glance, this seems counterintuitive, but in reality, it indicates that since oxidative stress levels are significantly lower in our centenarians, they have less need to produce antioxidant proteins to defend against it.”
Metabolic Health and Inflammation
Beyond oxidative stress, the study uncovered other significant findings. Certain regulatory proteins of the extracellular matrix maintain “youthful” expression levels in centenarians, while others may play a role in cancer defence. Proteins involved in fat metabolism, which typically increase sharply with age, rise far less in centenarians. The same trend applies to interleukin-1 alpha, a major inflammatory protein, which is also lower in this group.
Furthermore, the DPP-4 protein, which degrades GLP-1—a hormone that stimulates insulin secretion—remains well-preserved in centenarians. “By degrading GLP-1, DPP-4 helps maintain relatively low insulin levels, which could protect them against hyperinsulinism and metabolic syndrome,” notes Delhaes.
“This is also a counterintuitive mechanism, suggesting that centenarians maintain good glucose balance without needing to produce large amounts of insulin.”
Longevity thus appears to be linked to finely regulated metabolic health, where metabolism is optimized rather than intensified.
Implications for Healthy Living
The findings from this study could pave the way for new therapeutic approaches to combat frailty in the elderly population. “For now, our study highlights the importance of a healthy lifestyle, something we can all act upon,” the authors conclude. While genetics account for about 25% of longevity, lifestyle factors during adulthood play a significant role. This includes nutrition, physical activity, and social connections. For instance, consuming fruit in the morning can reduce oxidative stress throughout the day, while physical activity helps maintain a youthful extracellular matrix. Avoiding excess weight also preserves a healthy metabolism, similar to that observed in centenarians.
As researchers continue to unravel the mysteries of longevity, these insights underscore the importance of lifestyle choices in extending healthy years. The SWISS100 study not only enhances our understanding of ageing but also offers practical guidance for those seeking to improve their quality of life as they age.
