In Switzerland, only about 0.02% of the population reaches age 100. Researchers behind a major project called SWISS100 set out to answer a simple but powerful question: do these rare people carry biological clues that help explain their exceptional longevity?
A team from the University of Geneva (UNIGE) and the University of Lausanne (UNIL) says the answer looks like yes. By comparing blood proteins across age groups, they found that centenarians often show patterns that look surprisingly similar to much younger adults, especially in markers tied to oxidative stress, inflammation, and metabolism.
Their findings were published in Aging Cell in a study titled Plasma Proteome Profiling of Centenarian Across Switzerland Reveals Key Youth-Associated Proteins.
SWISS100
SWISS100 is described as the first large-scale Swiss research project dedicated to centenarians. Led by Daniela Jopp, a professor at UNIL, SWISS100 combines “four research strands” in sociology, psychology, medicine, and biology to understand longevity. The biological arm was directed by Karl-Heinz Krause, Professor Emeritus at UNIGE’s Faculty of Medicine.
The researchers focused on whether centenarians show molecular features that separate “normal aging” from what the team calls “exceptional aging.”
Methodology
The core idea was to compare blood protein profiles across three groups:
- 39 centenarians aged 100–105 (85% women)
- 59 octogenarians (and in the paper’s analytic sample, hospitalized geriatric patients aged 80–90)
- 40 younger healthy volunteers aged 30–60
Krause explained why the middle group matters: “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.”
To measure proteins at scale, the team used a proximity extension assay (PEA) on the Olink Explore platform, targeting inflammation and cardiometabolic proteins. They measured about 720 unique proteins, then applied quality control steps to remove outliers and account for site-related effects before comparing groups.
They used statistical testing to identify proteins that differed by age group, and fractional polynomial regression to capture patterns that change in non-linear ways across the lifespan. They also ran protein network and pathway analyses using tools such as STRING and Reactome to see what biological systems the “youth-like” proteins point toward.
The Headline Finding: 37 Proteins That Look “Young” in Centenarians
Out of the hundreds of proteins measured, the researchers highlight one striking result: across 37 proteins, centenarians had blood profiles closer to younger adults than to typical elderly patients.
Flavien Delhaes, first author and a researcher at UNIGE, said, “Of these 724 proteins, 37 produced a truly remarkable result.”
He added, “In our centenarians, the profiles of these 37 proteins are closer to those of the youngest group than to those of octogenarians.”
The team’s interpretation is not that centenarians avoid aging entirely. Instead, they argue that some key biological mechanisms appear to slow down in a way that helps preserve function and delay disease.
Less Oxidative Stress, and a Counterintuitive Clue
The clearest signal involved oxidative stress, often linked to aging because it can damage cells over time. The researchers focused on five proteins connected to oxidative stress and found centenarians had notably low oxidative stress markers.
Oxidative stress is tied to free radicals, which can rise due to chronic inflammation and dysfunctional mitochondria. Krause posed the key question: “Do centenarians produce fewer free radicals, or do they have a more powerful antioxidant defense?”
Then the team reported an answer that sounds backwards at first: centenarians had lower levels of certain antioxidant proteins than standard geriatric patients.
Krause explained why this may actually be good news: “The answer is very clear: centenarians have significantly lower levels of antioxidant proteins than the standard geriatric population.”
He added, “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.”
Mechanism in plain terms
If a body is generating fewer damaging free radicals in the first place, it does not need to keep revving up antioxidant defenses to fight the fallout. That can mean less wear-and-tear pressure across tissues over decades.
A “Younger” Extracellular Matrix: Keeping the Body’s Structure Strong
The study also flagged proteins involved in regulation of the extracellular matrix, described in the summary as the “cement” of the body. In centenarians, some of these regulators stayed closer to youthful levels.
That matters because the extracellular matrix helps hold tissues together and influences how organs maintain integrity. When it degrades or becomes disorganized, frailty, poor healing, and degeneration become more likely.
Mechanism in plain terms
If the body better maintains the scaffold that supports organs and blood vessels, it may resist the physical decline that often accelerates late in life.
Lower Inflammation and Fewer Metabolic Problems
Centenarians also showed a pattern of reduced inflammatory signaling and more stable metabolic regulation:
- Interleukin-1 alpha, described as a major inflammatory protein, was lower in centenarians.
- Several proteins involved in fat metabolism rose sharply with age in the standard geriatric population, but rose far less in centenarians.
One especially interesting protein was DPP-4, which degrades GLP-1, a hormone involved in insulin secretion and a key target in modern diabetes and obesity drugs.
Delhaes noted, “By degrading GLP-1, DPP-4 helps maintain relatively low insulin levels, which could protect them against hyperinsulinism and metabolic syndrome.”
He called it another surprising pattern: “This is also a counterintuitive mechanism, suggesting that centenarians maintain good glucose balance without needing to produce large amounts of insulin.”
Mechanism in plain terms
Instead of forcing the body to push out more insulin, centenarians may preserve glucose balance through tighter metabolic control. Lower chronic insulin levels may reduce metabolic strain, which can matter for diabetes risk, vascular health, and inflammation over time.
What the Pathway Work Suggests: Survival Systems That Stay Calmer and Smarter
When the team analyzed how these proteins connect, the “youth-like” set pointed toward several major biological systems:
- Responses to oxidative stress and detoxification of reactive oxygen species
- Immune and inflammatory signaling pathways
- Metabolic enzyme pathways
- Regulation of extracellular matrix stability
- Programmed cell death pathways and FOXO-related signaling
- Neurotrophic signaling pathways
The paper argues that this cluster view matters because longevity is not one magic protein. It is multiple systems staying better regulated, for longer.
How This Could Help Everyone Else
The authors say the long-term impact could include “new therapeutic approaches to combat frailty in the elderly population.” In other words, these proteins could become targets for treatments or monitoring tools aimed at keeping older adults healthier, not just alive.
But the researchers also emphasize something more immediate: lifestyle still appears to be the biggest lever most people can pull.
They write that “the genetic component of longevity accounts for only about 25%,” and that “lifestyle during adulthood is a powerful lever: nutrition, physical activity and social connections.”
They even give a simple example: “Eating a piece of fruit in the morning can reduce oxidative stress in the blood throughout the day.”
They add, “Physical activity helps maintain the extracellular matrix in a more ‘youthful’ state.”
And they point to weight control as another practical factor: avoiding excess weight helps preserve a healthier metabolism, closer to what they observe in centenarians.
The Swiss centenarians in SWISS100 did not appear to escape aging. Instead, they seemed to age with less oxidative stress, less inflammatory escalation, and more stable metabolic control. In a sense, their biology looks less like a machine being pushed harder, and more like one that is tuned better and maintained longer.
Or, as Delhaes put it, the results suggest that “certain key mechanisms are significantly slowed down.”
That combination, the researchers argue, may be the real signature of exceptional longevity: not one miracle trick, but a calmer internal environment that prevents damage from piling up year after year.
