Why do some centenarians age differently? What their metabolism reveals

Summary

Why do some people reach 100 while retaining good autonomy, whereas others develop age-related diseases early?

A new study offers part of the answer: centenarians display a particular metabolic signature, different from that seen in other older people.

These findings suggest that healthy ageing does not depend solely on genetics, but also on the functioning of several metabolic pathways involved in inflammation, energy production and hormonal regulation.

What is metabolism?

Metabolism encompasses all the chemical reactions that allow our body to function. At every moment, our cells produce thousands of molecules called metabolites. These molecules reflect the real state of our body.

Unlike genetics, which is relatively stable throughout life, the metabolome is influenced by:

• diet;
• physical activity;
• sleep;
• the gut microbiome;
• hormones;
• inflammation;
• the environment.

It thus provides a dynamic snapshot of our health status.

How was the study carried out?

The researchers analysed 1,495 metabolites present in blood samples. The initial study involved 213 participants:

• 70 centenarians;
• 80 children of centenarians;
• 63 people from families without exceptional longevity.

The results were then validated in several additional cohorts, bringing the total number of participants to more than 5,000 individuals. This approach considerably strengthens the robustness of the conclusions.

A genuine biological signature of ageing

The researchers identified around 360 metabolites whose concentration changes with age. In the majority of individuals, ageing is accompanied notably by:

• an increase in markers of oxidative stress;
• progressive dysfunction of the mitochondria (the « power plants » of cells);
• an increase in chronic inflammation;
• a decline in certain kidney functions.

These changes constitute what researchers call the classic metabolic signature of ageing.

What sets centenarians apart

Centenarians do not follow exactly this trajectory. The researchers identified 67 specific metabolites associated with exceptional longevity. Among them:

• several steroid hormones remain present at higher concentrations;
• certain molecules with anti-inflammatory properties are better preserved;
• some bile acids show a particular profile;
• several pathways involved in cellular energy production appear to work better.

These differences could explain why some people retain better health despite a very advanced age.

Inflammation: a major player in ageing

One of the most interesting findings concerns inflammation. Today, ageing is regarded as a state of low-grade chronic inflammation, sometimes called inflammaging.

In centenarians, researchers observe better regulation of this inflammation. This could help reduce the risk of many age-related diseases, notably:

• cardiovascular diseases;
• diabetes;
• frailty;
• certain neurodegenerative diseases.

Hormones also play a role

The study also shows that several steroid hormones decline much less in centenarians. These hormones are notably involved in:

• maintaining muscle mass;
• bone health;
• energy metabolism;
• cognitive functions;
• the immune response.

These results reinforce the idea that harmonious hormonal ageing could contribute to better longevity.

Can lifestyle make you a centenarian?

The answer is more nuanced. The authors recall that exceptional longevity probably depends on a complex combination of factors:

• genetics;
• environment;
• gut microbiome;
• diet;
• physical activity;
• sleep quality;
• absence of smoking;
• management of inflammation.

In other words, there is currently no intervention capable of guaranteeing a life expectancy of 100 years. On the other hand, many habits can increase the chances of ageing in better health.

What this study does not demonstrate

This publication does not allow us to conclude that:

• certain dietary supplements reproduce the metabolic profile of centenarians;
• a blood test can today accurately predict lifespan;
• correcting a single metabolite increases life expectancy.

This is an observational study that identifies associations, but does not demonstrate a causal link.

Future perspectives

Researchers now hope to identify the mechanisms responsible for these metabolic differences. In time, this work could lead to the development of:

• new biomarkers of biological ageing;
• tests to assess biological age more precisely;
• treatments targeting certain metabolic pathways;
• strategies aimed at slowing ageing and extending healthy lifespan.

These applications, however, remain to be confirmed by clinical trials.

The Valorian analysis

This study illustrates a major evolution in modern medicine: we are no longer talking only about life expectancy, but about healthy lifespan (healthspan).

Centenarians seem to share a remarkable ability to preserve several major biological balances: better-controlled inflammation, more efficient energy metabolism and better preservation of certain hormonal functions. These characteristics probably do not stem from a single factor, but from a complex interaction between genetics, lifestyle and the environment.

At Valorian, we consider that the goal is not only to live longer, but above all to preserve autonomy, physical and cognitive capacities, and a good quality of life. Knowledge from research on centenarians opens promising perspectives, but it also reinforces an essential message: daily habits — a balanced diet, regular physical activity, quality sleep, maintaining muscle mass and controlling cardiovascular risk factors — remain today the most effective interventions to promote healthy ageing.