To properly understand aging, it is necessary to understand what is slowly degrading in individual cells.
What causes our cells to become less efficient and more vulnerable to disease over time, until they begin to fail?
A new study, led by researchers at the Fritz Lipmann Institute (FLI) in Germany, and recently published in Nature Communications, reveals new clues about how cells’ powerhouses — organelles known as mitochondria — begin to slow down as the years go by.
Through nematode analysis Caenorhabditis elegansfrom human tissues and human cells, researchers identified that levels of a specific lipid molecule, phosphatidylcholine, decrease with age.
Experiments have also shown that restoring blood levels as phosphatidylcholine — through food, in laboratory models — can revitalize worn-out mitochondria.
“Our studies revealed decreased phosphatidylcholine synthesis as a conserved, previously unrecognized factor of natural mitochondrial aging that can be overcome with dietary supplements,” the researchers report.
One of the main functions of phosphatidylcholine is to maintain the membranes surrounding mitochondria in good condition. Like cell membranes, mitochondrial membranes are composed of lipids, such as phosphatidylcholine.
As levels of this lipid decrease, it has a direct effect on the functioning of mitochondria, researchers found.
But the addition of phosphatidylcholine or hill — a nutrient that is naturally converted to phosphatidylcholine — added to the nematodes’ diet returned the mitochondria to a younger, more flexible state.
“We ourselves were surprised by how strongly this molecule influences the structure, connectivity and function of mitochondria,” he says. Tetiana Poliezhaievacellular biologist at FLI and first author of the study, cited by .
Based on human tissue samples, lower levels of phosphatidylcholine were more common in people with diabetes or obesity, while higher levels corresponded with faster gait and better memory — signs associated with healthier aging.
Experiments comparing young, middle-aged and old nematodes showed that phosphatidylcholine levels decrease over time because the production of proteins that manufacture this lipid is gradually reduced as aging progresses.
As a result, mitochondria have fewer components available to form their membranes, becoming progressively more fragmented and dysfunctional.
In young organisms and healthy cells, mitochondria can easily fuse to form long, flexible chains that help the cell distribute energy and other resources.
However, experiments have shown that, with age and the lower presence of phosphatidylcholine, mitochondria become less flexible and less able to adapt to the cell’s energy needs.
“We can imagine the entire system as a finely branched electrical network that becomes increasingly damaged with age: connections break and currents become blocked”, he says. Maria Ermolaevacellular biologist at FLI.
“Although energy production continues, it becomes less efficient and sustainable, and energy can no longer be distributed flexibly.”
Analysis of human tissues also revealed a difference between men and women. In men, the fall in phosphatidylcholine levels was gradual; in women, it was much more pronounced — especially around menopause, which generally occurs between the mid-40s and mid-50s.
The researchers suggest that these chemical imbalances and subsequent changes in mitochondrial function may play a significant role at this stage of life.
“This observation is particularly relevant as it coincides with a time when many women report a significant decrease in energy levels and the onset of persistent fatigue,” says Ermolaeva.
The now-discovered reduction in phosphatidylcholine is not the only reason why our cells’ energy centers begin to wear out with age, but it appears to be an important contribution — and therefore something that scientists should investigate further.
And although humans are much more complex than nematodes, knowing that increasing levels of this lipid can mitigate some signs of mitochondrial aging in laboratory models is encouraging.
Next, the researchers want to examine in more detail how the drop in phosphatidylcholine levels affects mitochondrial membranes at the molecular level: how does the structure of these membranes change?
Mitochondria malfunction is linked to a wide range of diseases and chronic conditions, including diabetes, cancer, and neurodegenerative diseases such as Parkinson’s disease.
This work points to yet another possible way to alleviate some of the problems associated with the aging of mitochondria.
“Our work shows that both mitochondrial aging and broader systemic aging are, at least in part, modifiable,” says Ermolaeva. “If we understand the underlying processes, we may be able to take targeted countermeasures.”
