The dream of living a long life while remaining healthy and active for as long as possible has preoccupied humankind for centuries. Today, modern gerontology no longer attempts to explain this process solely in terms of lifestyle habits, but is increasingly investigating the biological mechanisms underlying healthy aging.
Why Some People Live to Be 100 or Older in Good Health
People who live to be 100 years old or older—so-called centenarians—are a special research group. They reach an age at which many people are already affected by several age-related diseases. Nevertheless, many centenarians remain functional for an astonishingly long time and show remarkable resilience to disease.
Scientists believe that this extraordinary longevity results from the interplay of various factors: genetic predisposition, environmental conditions, lifestyle, and biological defense mechanisms. While earlier research primarily examined the influence of genes and lifestyle habits, the immune system and metabolism are now also coming into sharper focus.
Two recent studies conducted as part of the New England Centenarian Study, involving researchers from Boston University and its partner institutions, provide new insights into the biological mechanisms that may help people stay healthy for exceptionally long periods. While one study analyzed the unique characteristics of the immune systems of centenarians, the second study focused on characteristic metabolic patterns in the blood that are associated with extreme longevity.
The Immune System of Centenarians: Protection Through Adaptability
The human immune system consists of a complex network of various cells and signaling pathways that recognize and combat pathogens and control damaged structures in the body. However, this system changes with age. This process is known as immune aging. As a result, the immune system’s ability to respond quickly and specifically to new threats declines. At the same time, chronic, low-grade inflammatory processes may increase—a condition associated with many age-related diseases such as cardiovascular disease, certain types of cancer, and neurodegenerative diseases. The researchers therefore asked themselves: What distinguishes the immune defenses of people who remain exceptionally healthy despite their advanced age?
A Detailed Analysis of Individual Immune Cells
A study published in 2023, led by scientists at Boston University’s Chobanian & Avedisian School of Medicine and Tufts Medical Center, examined precisely this question. The researchers analyzed blood samples from seven centenarians from the New England Centenarian Study, one of the largest studies of people with exceptional longevity in North America. They used a modern method: single-cell RNA sequencing. This technique makes it possible to examine individual cells in detail and determine which genes are active in each cell type.
The study focused on so-called peripheral blood mononuclear cells (PBMCs). This group includes various immune cells, such as:
- T cells, which can recognize infected or altered body cells,
- B cells, which produce antibodies,
- natural killer cells, which play a role in defending against certain tumor cells and viruses,
- monocytes and other immune cells that regulate inflammatory processes.
The researchers then compared the data from the centenarians with two other publicly available datasets to understand changes in the immune system across different age groups.
Centennials Have a “Trained”Immune System
The results showed that centenarians do not simply have an unchanged immune system. Instead, they exhibit certain adaptations that appear to be associated with greater resilience. The researchers found characteristic changes in the composition of various types of immune cells as well as in their gene activity. Of particular interest was the observation that the immune profiles of centenarians showed evidence of a long history of illness and successful immune responses. This means that these individuals’ immune systems appear to have learned to cope with stressors over the course of their lives. According to the scientists, it is precisely this ability that could be crucial. It is not the complete avoidance of illness that appears to be decisive, but rather the body’s ability to return to a stable state after experiencing stress. This characteristic is referred to as immune resilience.
Metabolism: A Biological Fingerprint for Healthy Aging
While the first study examined the immune system, another recent study focused on a different key aspect of the body: metabolism. Metabolism encompasses all the chemical processes through which the body generates energy, builds cells, regulates hormones, and responds to environmental factors. Metabolism changes with age. Some of these changes are associated with a higher risk of age-related diseases. The researchers therefore wanted to find out whether centenarians possess certain metabolic characteristics that distinguish them from other people.
For this study, the research team at Boston University analyzed blood samples from 213 participants in the New England Centenarian Study. The group included:
- 70 centenarians,
- their descendants,
- control subjects of comparable age.
Using a so-called non-targeted metabolomics approach, the scientists analyzed approximately 1,495 small molecules in blood serum. These molecules can provide clues as to which biological processes are particularly active in the body and how the organism adapts to aging processes. In addition, the researchers compared their results with four other metabolomics studies to determine whether certain patterns recur.
Distinctive Blood Markers in People With Exceptional Longevity
The analysis showed that centenarians have a characteristic metabolic profile. Changes were particularly noticeable in:
- certain bile acids,
- various steroids,
- other metabolites associated with cell protection, energy metabolism, and biological regulation.
These patterns differed from the changes that typically occur during the aging process. One particularly interesting finding: Some of these metabolic signatures were associated with longer survival time after blood collection. The researchers also developed a machine-learning model, a so-called “metabolomic clock.” In the future, this may help to more accurately estimate a person’s biological age. This is because actual age—that is, the number of years lived—does not always correspond to the biological state of the body.
Connection Between the Immune System and Metabolism
The two studies examine different areas of the body but reveal a similar underlying principle. Both the immune system and metabolism appear to be particularly flexible and stable in centenarians. A robust immune system helps the body cope with infections and other stresses. A well-regulated metabolism supports energy supply, cell repair, and the maintenance of vital bodily functions. Furthermore, the two systems influence one another. Metabolic byproducts can affect the activity of immune cells, while inflammatory processes, in turn, can alter metabolism. Researchers therefore suspect that healthy aging is not attributable to a single protective mechanism, but rather to a complex interplay of various biological processes.
An exceptionally long lifespan cannot be explained by a single factor. Scientists now believe that a complex interplay of genetic predispositions, biological protective mechanisms, and environmental factors determines how a person ages. In centenarians, certain processes in the body appear to be particularly resilient—including the immune system’s ability to adapt and the stability of key metabolic pathways. At the same time, studies show that a long and healthy life is not predetermined by genes alone. It is the interplay between genetic makeup, living conditions, and individual habits that influences how well the body can cope with stress and how long good health is maintained.
No Fountain of Youth – But Important Insights for the Future
Research on centenarians does not mean that there is a single method for living to be 100 years old. Nor do the findings provide direct guidance for medications or therapies. Nevertheless, they are of great significance to science.
The immune profiles and metabolic patterns of centenarians could help us better understand in the future why some people stay healthy longer. In the long term, this could lead to new approaches for detecting age-related diseases earlier or for extending healthy life expectancy—that is, the years people spend free of serious illness. Above all, centenarians demonstrate one thing to researchers: aging is not a uniform process. Some people apparently possess biological systems that remain more resilient and are better able to adapt to life’s challenges.
What Can Everyone Do to Age Healthily?
Although people cannot change their genes, many everyday decisions influence how healthily they age. Regular exercise is particularly important: Physical activity helps maintain muscle strength, flexibility, and bone density, improves cardiovascular health, and has a positive effect on metabolism, the brain, and the immune system. It doesn’t always have to be intense exercise—regular walking, climbing stairs, gardening, or other forms of natural movement can also make a valuable contribution.
Diet also plays a central role. A varied, predominantly plant-based diet rich in vegetables, fruits, legumes, whole grains, nuts, and high-quality protein sources provides the body with essential vitamins, minerals, fiber, and phytochemicals. At the same time, a balanced diet helps regulate metabolic processes and reduce risk factors such as obesity, high blood pressure, or elevated blood sugar levels. It is not individual “superfoods” that determine healthy aging, but rather the long-term quality of one’s overall diet.
Equally important are sufficient sleep and adequate periods of rest. During sleep, important repair and regulatory processes take place that influence, among other things, the immune system, memory function, and hormonal balance. Social relationships are also increasingly recognized in aging research as an important health factor. People with stable social connections, friendships, and regular mental stimulation often remain active longer and demonstrate greater psychological resilience.
In addition, regular preventive health screenings can help identify health risks early on. Well-controlled blood pressure, normal blood sugar levels, and healthy blood lipid levels protect the heart, blood vessels, and brain in the long term. Quitting smoking remains one of the most important modifiable factors for a longer and healthier life, as tobacco use contributes to numerous chronic diseases and can accelerate the aging process.
The findings from research on centenarians do not mean that aging can be completely controlled or that every person can reach an exceptionally advanced age. However, they do show that many factors collectively influence how well the body can cope with the challenges of aging and how long its functions are maintained.