Centenarians appear to age differently at the molecular level, maintaining unexpectedly “younger” biological signatures in key systems.

Only about 0.02% of people in Switzerland reach the age of 100. What sets these centenarians apart? Could their bodies hold clues to resisting the usual toll of aging? To investigate, scientists from the University of Geneva and the University of Lausanne analyzed blood samples from people across three age groups. What they found challenges the idea that aging is a steady, unavoidable decline.

The researchers, working within the “SWISS100” project, analyzed blood samples from centenarians, octogenarians, and adults aged 30 to 60. They identified 37 proteins in centenarians that closely resemble those found in younger individuals, especially those linked to low oxidative stress.

Some of these proteins are involved in maintaining the extracellular matrix (the “cement” of our body), while others may help protect against tumor development or regulate fat and sugar metabolism. The findings, published in Aging Cell, are part of a broader effort led by Daniela Jopp at UNIL, combining sociology, psychology, medicine, and biology to better understand longevity. The biological research, directed by Karl-Heinz Krause, focuses on the molecular traits that distinguish centenarians.

The study included 39 centenarians (aged 100–105, of whom 85% were women), 59 octogenarians, and 40 younger adults (aged 30–60). “The octogenarians allow a more fine-grained analysis of how certain blood markers evolve over a lifetime, and help to distinguish normal aging from the exceptional aging of centenarians,” explains the researcher.

Researchers measured 724 proteins in blood serum, including 358 linked to inflammation and 366 tied to cardiovascular health. “Of these 724 proteins, 37 produced a truly remarkable result,” says Flavien Delhaes. “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 aging, but that certain key mechanisms are significantly slowed down.”

Less oxidative stress

The researchers measured 724 proteins in blood serum, including markers linked to inflammation and cardiovascular health, both key factors in aging. Among these, 37 proteins stood out.

“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 aging, but that certain key mechanisms are significantly slowed down,” said Flavien Delhaes, the study’s first author.

Five of these proteins were tied to oxidative stress, a process driven by free radicals that can accelerate aging. Free radicals often arise from chronic inflammation, where immune cells produce them to fight threats, or from malfunctioning mitochondria that release excess harmful molecules.

Krause asked, “Do centenarians produce fewer free radicals, or do they have a more powerful antioxidant defense?” He added, “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.”

Fewer metabolic disorders and less inflammation

The study also found that proteins involved in maintaining the extracellular matrix appear at more youthful levels in centenarians, while some may contribute to cancer protection. Proteins linked to fat metabolism typically increase with age, but this rise is much smaller in centenarians. Levels of interleukin-1 alpha, a key inflammatory protein, are also lower in this group.

Another important finding involves the protein DPP-4, which breaks down GLP-1, a hormone that stimulates insulin production and is used in treatments for diabetes and obesity. In centenarians, DPP-4 remains well preserved. “By degrading GLP-1, DPP-4 helps maintain relatively low insulin levels, which could protect them against hyperinsulinism and metabolic syndrome,” Delhaes explained. “This is also a counterintuitive mechanism, suggesting that centenarians maintain good glucose balance without needing to produce large amounts of insulin.”

Overall, the results suggest that long life is linked to well-balanced metabolism rather than heightened activity.

Prioritizing a healthy lifestyle

In the long term, these findings 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. Since the genetic component of longevity accounts for only about 25%, lifestyle during adulthood is a powerful lever: nutrition, physical activity, and social connections. For example, eating a piece of fruit in the morning can reduce oxidative stress in the blood throughout the day. Physical activity helps maintain the extracellular matrix in a more ‘youthful’ state. And avoiding excess weight also helps preserve a healthy metabolism, similar to that observed in centenarians,” the authors conclude.