Gaining healthy years: How metabolism shapes the Aging process

Why does it become harder to maintain a healthy weight as we age? Why does the risk of diabetes or cardiovascular disease increase, even though many people lead healthier lifestyles than in the past? The answers often lie deep within our metabolism and our cells.

Although life expectancy is rising steadily, the number of chronic diseases is also increasing as we live longer. The crucial question is therefore: how can we live not just longer, but healthier lives?

This is precisely where the FWF-funded Cluster of Excellence “MetAGE” comes in. Under the leadership of Frank Madeo from the University of Graz, Deputy Director Thomas Scherer from the Medical University of Vienna, and Thomas Pieber from the Medical University of Graz, who heads MetAGE’s clinical trial programme, more than 70 researchers from the University of Graz, the Medical Universities of Graz and Vienna, and JOANNEUM RESEARCH are pooling their expertise.

“We do not view Aging in isolation at the level of individual organs,” explains Frank Madeo. “What is crucial is the interplay of metabolic processes throughout the entire organism.”

The research focuses on what is known as metabolic flexibility, i.e. the body’s ability to flexibly adapt energy production and storage to varying demands. With aging, this finely regulated system loses precision. Chronic inflammation increases, cellular self-cleansing (autophagy) declines, and mitochondrial function changes.

“When this adaptability declines, susceptibility to age-related diseases increases,” adds Thomas Scherer. “This is precisely where our research approaches come in.”

A key project within the cluster is the Pro-MetAGE study, which is being conducted jointly in Graz and Vienna. Among other things, it investigates how diet, controlled fasting or pharmacological interventions can influence metabolic processes.

“We need robust clinical data,” emphasises Thomas Pieber. “Only then can we develop concrete, evidence-based strategies for patients from promising molecular findings.”

The close integration of basic research and clinical application is considered a particular strength of the cluster. Findings from model organisms are systematically investigated in a clinical setting.

Aging is more than just a number

Whilst MetAGE deciphers the biological mechanisms of Aging, the Healthy Aging Center at the Medical University of Graz provides the clinical infrastructure for their long-term investigation and application.

After all, aging is more than just counting the years. Alongside chronological age, there is biological age. This describes the functional state of our body. Two people can be the same age yet age biologically differently.

“Biological age tells us how well our metabolism, organs and regulatory mechanisms are actually functioning,” explains Thomas Pieber. “It makes aging processes objectively measurable.”

A key focus here is on metabolic changes, which are considered central drivers of many age-related diseases. Being overweight plays a particularly significant role, though in a more nuanced way than the number on the scales might suggest.

Focus on body composition

The Healthy Aging Center therefore relies on precise diagnostics of body composition. Using the so-called “Bod Pod”, it is possible to determine exactly how much fat and muscle mass there is and how these change over time. In addition, the MetAGE clinical trial programme utilises modern whole-body MRI techniques to examine fat distribution on an individual basis. “Weight alone is not a sufficient marker of metabolic health,” explains Thomas Pieber. “What matters is how fat is distributed, whether muscle mass is maintained, and how these factors affect inflammatory and metabolic processes.”

This distinction provides crucial insights, particularly in the context of clinical trials. When testing new active substances or lifestyle interventions, the focus is not merely on weight loss, but on a sustainable improvement in metabolic health.

Research in dialogue with the public

The Healthy Aging Center sees itself as both a research platform and a clinical facility. Study participants receive a comprehensive analysis of their health status, ranging from metabolic parameters and body composition to biomarkers of biological Aging. There is considerable interest. Many people want to know what their biological age is and which factors they can actively influence.

Long-term observational studies play a central role in this. Only through continuous data collection over several years can ageing processes be validly analysed and effective preventive or therapeutic approaches developed.

A strategic field for the future in Graz

With the Healthy Aging Center, the Medical University of Graz is establishing healthy aging as an interdisciplinary cross-cutting theme – from basic molecular research and metabolic mechanisms to clinical application.

In close collaboration with the MetAGE cluster, this creates a research environment that combines international excellence with regional roots. Graz is thus positioning itself as a key hub for metabolic ageing research.

The core message remains clear: healthy aging is no accident. It is the result of complex biological processes – and, increasingly, of targeted scientific strategies.

Metabolism is at the heart of this. And with it comes the question of how many of our years we can spend in good health and with autonomy.