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The 'Swiss 100' study has identified 37 proteins in centenarians' blood whose profile appears linked to slower ageing.
In Switzerland, 0.02% of the population lives beyond the age of 100. 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 profiles of centenarians with those of octogenarians, and then with those of individuals aged 30 to 60. Across 37 proteins, centenarians show profiles surprisingly close to those of younger individuals, particularly with remarkably low oxidative stress markers. Among the other proteins identified, at least three are involved in the regulation of the extracellular matrix (the "cement" of our body). Others could play a protective role against tumour development or be involved in lipid and glucose metabolism. These findings are published in the journal Aging Cell.
Led by Daniela Jopp, Professor at UNIL, "SWISS100" combines four research strands – sociology, psychology, medicine and biology – to unlock the secrets of longevity. The biological component, directed by Karl-Heinz Krause, Professor Emeritus at the UNIGE Faculty of Medicine, focused specifically on the molecular characteristics of Swiss centenarians. His team compared three groups: 39 centenarians (aged 100–105, of whom 85% were women), 59 octogenarians and 40 much younger volunteers (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 ageing from the exceptional ageing of centenarians," explains the researcher.
Oxidative stress levels are significantly lower in our centenarians.
Less oxidative stress
The scientists measured 724 proteins in blood serum, including 358 inflammatory markers and 366 cardiovascular markers – two areas that are critical for longevity. "Of these 724 proteins, 37 produced a truly remarkable result," highlights Flavien Delhaes, researcher at the Department of Cell Physiology and Metabolism at the UNIGE Faculty of Medicine and first author of the study. "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 clearest results concern five proteins linked to oxidative stress, suspected of accelerating ageing. Oxidative stress, caused by free radicals, stems mainly from two sources: chronic inflammation, where white blood cells produce free radicals to defend the body, and dysfunctional mitochondria which, like poorly maintained old cars, release these molecules whose overproduction becomes harmful. "Do centenarians produce fewer free radicals, or do they have a more powerful antioxidant defence?" adds Karl-Heinz 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."
Fewer metabolic disorders and less inflammation
Among other significant findings, certain regulatory proteins of the extracellular matrix show "youthful" expression levels in centenarians, while others could play a role in cancer defence. Several proteins involved in fat metabolism increase sharply with age in the standard geriatric population, but far less so in centenarians. The same applies to interleukin-1 alpha, a major inflammatory protein, which is also lower in the latter group.
Furthermore, the DPP-4 protein, which degrades GLP-1 (a hormone that stimulates insulin secretion and forms the basis of new drugs against diabetes and obesity), 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," points out Flavien 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 optimised rather than intensified.
Prioritising 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.
