🩸 Longevity: The Blood of Centenarians Speaks

The "Swiss 100" study identified in the blood of centenarians 37 proteins whose profile appears to be linked to slowed aging.

In Switzerland, 0.02% of the population is over 100 years old. Could there be biological characteristics associated with this exceptional longevity? As part of the "SWISS100" study, the first large-scale Swiss research project dedicated to centenarians, a team from the University of Geneva (UNIGE) and the University of Lausanne (UNIL) compared the blood profile of centenarians with that of octogenarians, and then with that of people between 30 and 60 years old.


For 37 proteins, centenarians show a profile surprisingly close to that of younger individuals, notably with particularly low markers of oxidative stress. Among the other proteins identified, at least three are involved in regulating the extracellular matrix (the "cement" of our body). Others could play a protective role against tumor development or be involved in lipid and glucose metabolism. These results are published in the journal Aging Cell.

Led by Daniela Jopp, a professor at UNIL, "SWISS100" combines four research areas - sociology, psychology, medicine, and biology - to unravel the secrets of longevity. The biological component, led by Karl-Heinz Krause, honorary professor at the Faculty of Medicine of UNIGE, specifically examined the molecular characteristics of Swiss centenarians. His team thus compared three groups: 39 centenarians (100-105 years old, 85% women), 59 octogenarians, and 40 much younger volunteers (30-60 years old). "Octogenarians allow for a finer analysis of the evolution of certain blood markers throughout life and help distinguish normal aging from the exceptional aging of centenarians," says the researcher.

The level of oxidative stress is significantly lower in our centenarians.

Less Oxidative Stress

The scientists measured 724 proteins in the blood serum, including 358 markers of inflammation and 366 cardiovascular markers, two key areas for longevity. "Out of these 724 proteins, 37 showed a truly astonishing result," emphasizes Flavien Delhaes, a researcher in the Department of Cell Physiology and Metabolism at the Faculty of Medicine of UNIGE and the study's first author. "In our centenarians, the profiles of these 37 proteins are closer to those of young people than to those of octogenarians. This represents about 5% of the measured proteins, which suggests that centenarians do not completely escape aging, but that some key mechanisms are strongly slowed down."

The clearest results concern five proteins linked to oxidative stress, suspected of accelerating aging. Oxidative stress, caused by free radicals, comes mainly from two sources: chronic inflammation, where white blood cells produce free radicals to defend the body, and dysfunctional mitochondria which, like old, poorly maintained cars, release these molecules whose overproduction then becomes harmful.

"Do centenarians produce fewer free radicals or do they have a more powerful antioxidant defense?" adds Karl-Heinz Krause. "The answer is very clear: centenarians have significantly reduced levels of key antioxidant proteins. At first glance, this seems counterintuitive, but in reality, it indicates that since the level of oxidative stress is significantly lower in our centenarians, they therefore have less need to produce antioxidant proteins to defend themselves."

Fewer Metabolic Disorders and Less Inflammation

Among other significant discoveries, some proteins that regulate the extracellular matrix show "young" expression levels in centenarians, while others could play a role in defense against cancer. Several proteins involved in fat metabolism increase strongly with age in the standard geriatric population, but much less so in centenarians. The same goes for interleukin-1 alpha, a major inflammatory protein, also lower in the latter.

Furthermore, the protein DPP-4, which degrades GLP-1 (a hormone stimulating insulin secretion, the basis of new drugs for diabetes and obesity), is well preserved in centenarians. "By degrading GLP-1, DPP-4 helps maintain relatively low insulin levels, which could protect them from hyperinsulinemia and metabolic syndrome," notes Flavien Delhaes. "This is a counterintuitive mechanism suggesting that centenarians maintain good glucose balance without needing to produce a lot of insulin." Longevity thus seems to be linked to finely regulated metabolic health, where metabolism is optimized rather than intensified.

Prioritize a Healthy Lifestyle

In the long term, these results 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, which we can all act upon. The genetic component of longevity being only about 25%, lifestyle during adulthood is a powerful lever: nutrition, physical activity, social contacts.

For example, consuming a fruit in the morning can reduce blood oxidative stress during the day. Physical activity helps keep the extracellular matrix in a more 'youthful' state. Avoiding overweight also helps preserve a healthy metabolism, similar to that observed in centenarians," conclude the authors.