In most people, the proteins that keep cells resilient—regulating immunity, energy, and inflammation—gradually drift out of balance with age. However, among centenarians in a new Swiss study, 37 of those proteins remained youthful.
The Biology of Aging—Why It Varies
Aging affects everyone differently. Although many older adults face chronic disease and frailty, some remain remarkably healthy well into their 100s. Scientists have long suspected that genes deserve much of the credit. New research suggests that the answer is more specific and more actionable than that.
The study, published in Aging Cell, analyzed the blood of centenarians and compared their immune and cardiometabolic protein profiles with those of healthy adults aged 30 to 60 and with those of hospitalized older adults aged 80 to 90. Using proteomics, a technique that measures hundreds of proteins at once, the team examined how protein levels shift across the lifespan to identify pathways that may explain exceptional resilience in extreme old age.
The centenarians had 583 proteins expressed at different levels from those in the two other groups. Among those proteins, 37 stood out for maintaining levels closer to those of younger adults than those of typical older adults—a pattern that aligned with findings from other large centenarian studies and established aging biomarkers.
“This study reinforces a central principle in longevity science: Exceptional aging does not mean escaping biological decline, but selectively preserving key regulatory mechanisms,” Sou Ahdjoudj Orlando, a longevity scientist and founder of AION Life, who was not involved in the study, told The Epoch Times.
The Biological Systems That Refuse to Age
The 37 proteins clustered around five key biological processes:
1. Cell Clearance
Six of the proteins clustered around apoptosis, the process that clears damaged cells. Efficient removal of dysfunctional “zombie” cells may help prevent chronic inflammation and reduce cancer risk.
2. Oxidative Stress
Five proteins related to oxidative stress were expressed at lower levels in centenarians, a finding that initially seemed counterintuitive. Lower antioxidant protein levels likely signal that cells are experiencing less stress to begin with, not that their defenses are failing, Orlando said, calling it “a signature of resilience rather than resistance.”
Dr. Gabriel Alizaidy, a longevity and precision medicine expert, noted that four of the 37 proteins—SOD1, PRDX3, HMOX1, and GLRX—point toward mitochondrial protection. Mitochondria generate energy but also produce reactive oxygen species that accumulate and damage cells over time. When they work efficiently, they deliver steady energy while producing fewer harmful molecules, helping limit cellular damage, particularly in energy-demanding tissues such as the brain cells.
“These four proteins clean that up through different mechanisms, and the fact that all four held at youthful levels together in centenarians tells you that mitochondrial resilience isn’t a side note in exceptional aging but a central and consistent theme of it,” Alizaidy said.
3. Tissue Integrity and Glucose Control
Proteins that support cells and help keep them in place formed another cluster, potentially contributing to structural tissue integrity and possibly cancer defense.
Within this group, DPP-4, an enzyme that breaks down glucagon-like peptide-1, a hormone that stimulates insulin release, was preserved in centenarians. Although this may seem counterintuitive given insulin’s role in lowering blood sugar, the authors suggest that centenarians may maintain glucose balance without excessive insulin signaling, reflecting a finely tuned rather than overactive metabolism.
4. Energy Regulation
Another cluster covered metabolic regulation, including proteins that help manage energy balance and glucose control. One of those, adenylate kinase 1, regulates AMPK, a cellular energy sensor that activates when energy is low, helping cells conserve resources.
“If you’ve heard of metformin, berberine, or the metabolic benefits of exercise and caloric restriction, you’ve heard of things that work partly through AMPK activation,” Alizaidy said.
5. Brain and Immune Health
Other clusters were linked to neurotrophic signaling—pathways that support nerve cell survival and brain function—and immune regulation, reinforcing the idea that exceptional longevity may depend on preserving balance across multiple biological systems simultaneously.
Alizaidy noted that the study was small and observational, meaning that it cannot establish cause and effect. The protein panels were also limited to inflammation and cardiometabolism.
“We don’t know if these proteins are driving exceptional longevity or simply reflecting a biological system that was already running well for other reasons,” he said, but he also said that the direction of the findings aligns with other independent centenarian datasets.
Lifestyle Still Matters
Although genetic endowment may set the stage, how people live over decades is still a dominant factor.
“The centenarians in this study were the product of decades of a system running cleaner than average,” Alizaidy said. “And most of that comes down to how they lived.”
Orlando identified three biological principles that map directly onto the biological patterns preserved in the centenarians:
- Metabolic Stability: Resistance training, daily movement, adequate protein intake, and avoiding chronic overnutrition help maintain steady glucose control and hormonal balance.
- Reduced Inflammation: Restorative sleep, a healthy body composition, and a fiber-rich, nutrient-dense diet help reduce systemic inflammatory load over time.
- Mitochondrial Health: Regular physical activity, stress management, and avoiding smoking and excessive alcohol support lower oxidative stress and cellular resilience.
Some Food and Drug Administration-approved therapies already act on pathways linked to resilience, Alizaidy added. He pointed to the SS-31 peptide, an investigational drug that supports mitochondrial function, and lower-dose glucagon-like peptide-1 agonists, which are Food and Drug Administration-approved for diabetes and weight management and which may help maintain metabolic balance, with improvements seen in lipid levels, blood sugar, and inflammation even without weight loss.
Orlando noted that the findings require larger, long-term validation, but he said that they add to growing evidence that longevity depends on preserving key biological systems over time.
“Longevity may ultimately depend less on eliminating aging, and more on identifying and preserving the biological systems that age more slowly,” he said.