Pre-eclampsia, a condition that strikes up to one in twelve pregnancies around the world and stands behind roughly a sixth of maternal deaths, has long been understood mainly through its damage. A team led by Flinders University, working with the Robinson Research Institute in Adelaide, has begun asking a older question: what sets that damage in motion. Their findings suggest that the placenta, the organ that quietly sustains a child before birth, may age ahead of its time, and that this ageing may be something that drives the illness rather than only following from it. The work remains in the
Prematurely Ageing Placentas May Help Explain Pre-eclampsia, Study Finds
Pre-eclampsia affects up to 8% of pregnancies worldwide and contributes to about 16% of maternal deaths globally.
Placental ageing may be a driver of pre-eclampsia, not just a consequence
Mark
Why does it matter that the placenta ages early, rather than just being damaged?
Mimi
Because it shifts the question from what pre-eclampsia does to the placenta toward what may be driving it. Dr Arthurs describes ageing as possibly contributing to the disease, not just following from it.
Luke
Careful with 'contributing'. The tissue came from pregnancies already affected by late-onset pre-eclampsia. Does that prove ageing comes first?
Mimi
The source doesn't claim proof. Dr Arthurs says ageing 'may be' an important process, which is hedged language.
Mark
What did they actually find in the tissue?
Mimi
More DNA damage, shortened telomeres, and a build-up of aged cells that no longer function normally.
Luke
And the oxidative stress piece?
Mimi
They identified it as a major contributor, and reducing it in lab-grown mini-placentas lessened several ageing markers.
Luke
That's in organoids, not in pregnant women. Nothing here says it would work in a person.
Mark
What about TERRAs?
Mimi
Levels were lower in affected placentas, and lowering them in the lab models made ageing signs stronger.
Luke
Which is suggestive. Whether it leads to treatments or earlier screening is unknown; the researchers say more research is needed first.
The Pulse
- Pre-eclampsia threatens up to 8% of pregnancies worldwide, and its gravest outcome is a leading cause of maternal death.
- Placentas from affected pregnancies are showing signs of premature ageing: damaged DNA, shortened chromosome caps, and clusters of exhausted cells.
- Oxidative stress is emerging as a central culprit, and calming it in lab-grown mini-placentas softened several ageing markers.
- Lower levels of protective TERRA molecules add a second thread, and the researchers are now charting whether these pathways can become treatment targets, though the work is still preclinical.
Pre-eclampsia, a condition that strikes up to one in twelve pregnancies around the world and stands behind roughly a sixth of maternal deaths, has long been understood mainly through its damage. A team led by Flinders University, working with the Robinson Research Institute in Adelaide, has begun asking a older question: what sets that damage in motion. Their findings suggest that the placenta, the organ that quietly sustains a child before birth, may age ahead of its time, and that this ageing may be something that drives the illness rather than only following from it. The work remains in the laboratory and in tissue samples, but it points toward pathways that might one day protect mothers and babies before a crisis arrives.
For a woman diagnosed with pre-eclampsia, the treatment that works is often the hardest one: delivering the baby, even when the pregnancy has not reached full term. The condition touches up to 8% of pregnancies worldwide and contributes to about 16% of maternal deaths, which makes it one of the most serious complications a pregnancy can carry.
Researchers at Flinders University, with colleagues at the Robinson Research Institute, have started to ask why it begins. Their central idea is that the placenta may age too quickly, and that this ageing could be an active force in the disease rather than just its result. The placenta delivers oxygen and nutrients to the baby and carries away waste, so when it falters, the danger to both mother and child grows.
The team studied placental tissue from healthy pregnancies and from those affected by late-onset pre-eclampsia, and also grew miniature placentas in the laboratory. The affected placentas showed more DNA damage, shorter telomeres, and a build-up of aged cells that no longer function. Oxidative stress stood out as a major contributor, and when the researchers reduced it in their models, several signs of ageing eased.
The team also found lower levels of TERRA molecules, which help protect chromosome ends, in affected placentas. Reducing TERRA in the models intensified the signs of cellular ageing. The work is not yet ready for clinical use, but the researchers hope these pathways could one day support prevention, earlier identification of at-risk pregnancies, and better care.
For a woman diagnosed with pre-eclampsia, the treatment that works is often the hardest one: delivering the baby, even when the pregnancy has not reached full term. The condition affects up to 8% of pregnancies worldwide and contributes to about 16% of maternal deaths globally, which places it among the most serious complications of pregnancy.
New research led by Flinders University, in collaboration with the Robinson Research Institute at Adelaide University, offers a clue about why it happens. The finding is that the placenta may age prematurely. The team also identified biological pathways that could, in time, help protect mothers and babies.
The lead author, Dr Anya Arthurs of the Flinders Health and Medical Research Institute, says the study goes past the observation that a placenta is damaged and asks what may cause the damage. In her words, placental ageing may be an active process that contributes to pre-eclampsia, rather than simply a consequence of the disease. Earlier work had linked placental ageing to pregnancy complications, she says, but the group wanted to understand what pushes a placenta to age too soon.
The placenta is a baby's lifeline during pregnancy. It supplies oxygen and nutrients and carries away waste, and when it falters, the risks to mother and baby rise significantly.
To investigate, the researchers examined placental tissue from healthy pregnancies and from pregnancies affected by late-onset pre-eclampsia. They also used laboratory-grown mini-placentas, known as trophoblast organoids, to look at the condition in finer detail.
Placentas from pre-eclamptic pregnancies showed several signs of accelerated ageing: more DNA damage, shortened telomeres (the caps that protect chromosomes), and a build-up of aged cells that no longer work normally.
Oxidative stress emerged as a major contributor. It occurs when harmful molecules accumulate faster than the body's natural defences can clear them, damaging cells and tissues. Dr Arthurs says that as oxidative stress rises, placental cells accumulate damage that appears to speed ageing. She calls it particularly encouraging that reducing oxidative stress in the laboratory models lessened several markers of placental ageing.
The study also pointed to molecules called telomeric repeat-containing RNAs, or TERRAs, which help protect chromosome ends and keep cells functioning well. Levels were lower in placentas affected by pre-eclampsia, and when the researchers lowered TERRA levels in laboratory models, the signs of cellular ageing became more pronounced.
The work is preclinical. The researchers say more research is needed before any new therapy can be used in pregnancy, but they believe the pathways identified could eventually support better prevention, earlier identification of at-risk pregnancies and improved care.
The paper, 'Late-Onset Pre-eclampsia is characterised by Accelerated Placental Aging', was published in PNAS. Its authors include Arthurs, Rudrarup Bhattacharjee, Melanie D Smith, Dulce L Medina Garcia, Ellen Menkhorst, German Mora, Jessica M Williamson, Lynda K Harris of the University of Nebraska, Jose M Polo, David A MacIntyre and Claire T Roberts. Funding came from Flinders University, the Flinders Foundation, Firefly, the University of Adelaide, an NHMRC Investigator Grant and the US National Institutes of Health.
Notable Quotes
Placental ageing may be an important process that contributes to pre-eclampsia, rather than simply a consequence of disease.— Dr Anya Arthurs, Flinders Health and Medical Research Institute
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