Phosphatidylcholine Could Help Reverse Mitochondrial Ageing

To understand ageing properly, we need to examine what gradually comes undone inside individual cells.

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

Phosphatidylcholine and mitochondrial ageing

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

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

Their tests further indicated that replenishing phosphatidylcholine through diet can reinvigorate tired 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.

One of phosphatidylcholine’s key functions is to maintain the membranes surrounding mitochondria. Mitochondrial membranes, like cell membranes, are built from lipids including phosphatidylcholine.

The researchers found that as this lipid becomes less available, mitochondrial performance within cells is directly affected.

When the scientists added either phosphatidylcholine or choline - a nutrient naturally converted into phosphatidylcholine - to the worms’ food, the mitochondria regained a younger, more 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 lipids disrupt cell energy

Comparisons between young, middle-aged and old worms revealed that phosphatidylcholine diminishes over time because production of the proteins required to make the lipid is gradually reduced as ageing advances.

Mitochondria consequently have less material available for building their membranes, leaving them progressively more fragmented and less functional.

During early stages of life and in healthy cells, mitochondria can easily merge into long, flexible chains, helping cells distribute energy and other resources.

The experiments showed, 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."

Human tissue samples suggested that lower phosphatidylcholine levels were more frequent among people with diabetes or obesity. Higher concentrations, meanwhile, were associated with a faster walking pace and stronger memory, both indicators of healthier ageing.

Differences in phosphatidylcholine decline between women and men

The human tissue findings also uncovered a difference between women and men in the fall of phosphatidylcholine. Levels declined gradually in men, but the reduction was substantially sharper in women, particularly around the age of menopause, which typically occurs from the mid-40s to the mid-50s.

The scientists propose that these chemical imbalances, along with the resulting changes to mitochondrial function, may have an important role at this point in 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.

The newly identified decrease in phosphatidylcholine is not the sole reason cellular power stations deteriorate with age. Nevertheless, it appears to be an important factor that warrants further scientific investigation.

Although humans are considerably more complex than worms, the finding that increasing this missing lipid may reverse certain signs of mitochondrial ageing is promising.

The researchers next plan to investigate more closely how lower phosphatidylcholine levels alter mitochondrial membranes at the molecular scale, including how the structure of these membranes changes.

Faulty mitochondria are linked to numerous illnesses and chronic conditions, including diabetes, cancer and neurodegenerative diseases such as Parkinson’s.

This research highlights another potential route for addressing some of the difficulties caused by 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 study was published in Nature Communications.