Even those who feel as if they could uproot trees today will eventually notice: Around age 60, there are some significant changes in the body. "Between the ages of 60 and 70, most people increasingly notice that their energy is waning," Herrmann explains. "It might be enough for a hike, but sprinting becomes difficult, as do new mental feats. Learning a new language is often no longer an option." The body simply can no longer muster the necessary energy. In other words: It is growing old.
According to the cell biologist, aging is genetically determined and primarily caused by wear and tear in our cells, specifically in certain cellular organelles called mitochondria. These cellular powerhouses contain a biological timer. "The individual cellular program is predetermined. There is a biological limit of 90 to 95 years, unless you have very fortunate genes." Significantly extending life beyond that point is therefore unrealistic, at least without genetic intervention.
Cell biologist Herrmann is investigating the exact role that mitochondria play in aging and why their performance declines over the course of a lifetime. The European Research Council (ERC) is supporting his basic research with an Advanced Grant. This prestigious funding is aimed at scientists who are leaders in their field and whose research promises fundamental breakthroughs.
“The cellular aging program has little to do with classic signs of wear and tear,” explains Herrmann. "Of course, eyes, bones, and joints wear out. But many organs, such as the brain and muscles, are fundamentally capable of constantly repairing their components. Our nerve cells are just as old as we are. We don’t produce new ones. The ones we have were formed in our mother’s womb and during early childhood development, and they generally function stably for decades because they continuously renew themselves."
This robust system doesn’t function for 120, 150, or more years because the energy balance of the mitochondria eventually becomes imbalanced due to genetic programming, typically after 70 to 90 years in humans.
Herrmann compares this process to the development of an unborn child: "A pregnancy lasts nine months. There’s little we can do to change that unless we alter the human genetic blueprint. It’s similar with individual lifespan. The aging process in humans is so strictly predetermined that you can look someone in the face and pretty accurately tell how old they are.”
Herrmann explains the biological process behind it: "Mitochondria consist of hundreds of proteins. These must be assembled precisely to produce energy-generating enzymes." For decades, mitochondria reliably supply more energy than the body needs. However, over time, this finely tuned system falls out of sync.
Herrmann suggests that accumulations of proteins in the cytosol may be a possible explanation for this. The cytosol is the fluid space inside the cell that surrounds the mitochondria. "Such protein aggregates, which we also see in diseases like Alzheimer's and Parkinson's, are linked to mitochondrial performance."
Many proteins destined for the mitochondria are first produced in the cytosol and then taken up by the mitochondria. Herrmann’s team has discovered that this import process works quickly and reliably when the mitochondria are healthy.
However, in defective mitochondria, uptake slows down, leaving proteins in the cytosol. Some of these proteins then send signals to the cell nucleus, triggering repair processes. "This intracellular communication acts like a quality control mechanism to ensure that the mitochondria remain functional. The efficiency of this process is an important factor in the aging process,” explains Herrmann, whose research aims to improve our understanding of these connections.
Modern technology enables new insights. The researchers can peer inside cells using high-resolution microscopy. Using live-cell imaging, they observe protein aggregates in living yeast cells in real time. "In addition to this fascinating method, mass spectrometry is a huge breakthrough for us," says Herrmann. It allows them to analyze thousands of molecules simultaneously, providing detailed insights into a cell’s protein structure. Among other things, the researchers have uncovered a striking pattern: During aging, entire groups of proteins begin to aggregate rather than individual proteins. “We don’t yet know exactly why this is the case.”
Herrmann’s research group has also found that some cells are more robust than others. Therefore, the aging process does not affect all cells equally. "In a nerve pathway, for example, where many cells work in sequence, the organism can compensate for damage to individual cells for a long time." But when too many cells fail, the effect becomes noticeable. Then, relatively suddenly, typical signs of aging, such as impaired hearing and vision or increased fatigue, appear – which explains why many people feel old 'all at once.'” Muscles and tissues weaken, and the likelihood of developing neurodegenerative diseases, such as Alzheimer’s or Parkinson’s, as well as metabolic diseases, increases.
Are we helplessly at the mercy of aging? We shouldn't make it that simple. The fact that life expectancy has risen significantly in many countries over the past few decades shows just how much room for improvement there is. Improved living conditions, medical advances, and healthier lifestyles mean that many people today live longer than in the past.
Ultimately, it's less about stopping aging and more about making the most of one's lifespan in a healthy way. "It's relatively easy to do things that prevent you from living as long as you could," says Herrmann. People who smoke a lot, overeat, and don’t exercise have a good chance of not reaching 90,” says Herrmann. He emphasizes the well-known principles of a healthy lifestyle, such as maintaining a balanced diet. He takes a nuanced view of trends like intermittent fasting. Whether such methods extend lifespan has not been conclusively proven. However, they could certainly have positive health effects.
"Of course, there is a lot you can do to ensure you remain reasonably healthy well into old age," says Herrmann. The important thing is not the dream of eternal life but rather staying active and healthy for as long as possible.
Here are some recommended readings:
Krämer L, Dalheimer N, Räschle M, Storchova Z, Pielage J,, Boos F, Herrmann, JM (2023). MitoStores: chaperone-controlled protein granules store mitochondrial precursors in the cytosol. EMBO J 42, 1-18.
Song J, Herrmann JM, Becker T (2021). Quality control of the mitochondrial proteome. Nat Rev Mol Cell Biol. 22, 54-70.
Boos F, Labbadia J, Herrmann JM (2020). How the mitoprotein-induced stress response safeguards the cytosol: A unified view. Trends Cell Biol. 30, 241-254.
