Phosphatidylcholine May Help Reverse Mitochondrial Ageing, Study Finds

To understand ageing properly, we need to examine the gradual processes coming undone within individual cells.

Why do cells become less effective and more prone to disease as time passes, before ultimately failing?

Phosphatidylcholine and mitochondrial ageing

A new study led by scientists at Germany’s Fritz Lipmann Institute (FLI) offers fresh insight into why mitochondria – the organelles that act as cells’ energy-producing engines – lose speed over the years.

By studying worm models, human tissue and human cells, the team found that concentrations of a specific lipid, or fat molecule, called phosphatidylcholine fall with age.

Their tests further indicated that replenishing phosphatidylcholine through diet can restore vitality to struggling mitochondria.

"Our studies revealed a decline in phosphatidylcholine synthesis as a previously unappreciated, conserved driver of natural mitochondrial aging, which can be overcome by dietary supplements," the researchers report.

A key role of phosphatidylcholine is maintaining the membranes that surround mitochondria. As with cellular membranes, mitochondrial membranes contain lipids including phosphatidylcholine.

The researchers found that dwindling supplies of this lipid directly impair how effectively mitochondria function inside cells.

Yet when the worms were given phosphatidylcholine or choline – a nutrient naturally converted into phosphatidylcholine – in their food, their mitochondria regained a more youthful and adaptable condition.

"We were surprised ourselves by how strongly this molecule influences the structure, connectivity, and function of mitochondria," says FLI cell biologist Tetiana Poliezhaieva, first author of the new study.

How declining lipid levels affect cells

Human tissue samples showed that lower phosphatidylcholine levels were more frequently found in people with diabetes or obesity. Conversely, higher levels were linked with a quicker walking pace and stronger memory, both markers of healthier ageing.

Comparisons between young, middle-aged and old worms revealed that phosphatidylcholine levels decrease because production of the proteins responsible for making the lipid is progressively reduced as ageing advances.

Consequently, mitochondria have less material available for constructing their membranes, becoming more fragmented and less functional over time.

During early stages of life and in healthy cells, mitochondria can normally fuse easily, creating long and flexible chains that enable cells to distribute energy and other resources.

The experiments found, however, that ageing and reduced phosphatidylcholine make mitochondria less adaptable and less capable of responding to a cell’s energy requirements.

"You can imagine the whole system as a finely branched power grid that becomes increasingly damaged with age: connections break down, and currents stall," says cell biologist Maria Ermolaeva, from the FLI.

"Although energy production continues, it becomes less efficient and sustainable, and energy can no longer be distributed flexibly."

The human tissue findings also uncovered a difference between men and women in the fall in phosphatidylcholine. For men, the reduction was gradual; for women, it was considerably steeper, particularly at around menopausal age, typically from the mid-40s to the mid-50s.

The researchers propose that these chemical imbalances, and the resulting alterations to mitochondrial function, may have an important role during this period of life.

"This observation is particularly noteworthy, as it coincides with a time when many women report a significant decline in energy levels and the onset of persistent fatigue," says Ermolaeva.

Potential ways to address mitochondrial decline

The newly identified fall in phosphatidylcholine is not the sole cause of the age-related deterioration of cells’ power stations, but it seems to be a substantial factor and warrants further scientific investigation.

Although humans are far more complex than worms, the finding that increasing this depleted lipid might reverse certain signs of mitochondrial ageing is promising.

The researchers next intend to investigate more closely how reduced phosphatidylcholine changes mitochondrial membranes at a molecular scale, including how their structure is altered.

Faulty mitochondria are associated with numerous illnesses and long-term conditions, including diabetes, cancer and neurodegenerative diseases such as Parkinson’s.

The study identifies another possible route for correcting some of the issues affecting ageing 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."

The research was published in Nature Communications.