Pre-eclampsia accelerates ageing in women

Pre-eclampsia is a puzzling sickness marked by a potentially fatal rise in blood pressure. Every year, it claims the lives of about 70,000 women globally. Scientists lack particular treatment plans because they do not know what causes it.

Vesna D Garovic, MD, Ph, a nephrologist at Mayo Clinic in Rochester, Minnesota, who has devoted her career to investigating this common pregnancy issue, says that delivery, the only treatment option, is not the cure it is frequently made up to be.

"Even after delivery, women can have dangerously high blood pressure for many days or weeks," she said.

"And they remain at an elevated risk for cardiovascular and kidney disease decades later."

Dr Garovic has demonstrated through a mix of epidemiological studies and laboratory trials that women with pre-eclampsia experience an accelerated ageing state that sets them on the route to acquiring age-related illnesses like heart attack, stroke, and kidney failure.

Her work is elucidating a potential mechanism of pre-eclampsia that may eventually lead to the development of the first treatments intended to address the condition's fundamental causes. It also emphasises how crucial it is to screen and treat pre-eclamptic women more thoroughly.

The organ that develops with each pregnancy to protect and nourish the growing baby, the placenta, is the basis for the majority of pre-eclampsia studies.

Pre-eclampsia is thought to be caused by the placenta secreting substances into the mother's bloodstream that promote inflammation and obstruct the angiogenesis, or growth of new blood vessels, process. They contend that these dangerous chemicals lead to systemic illness in pregnant women.

According to Dr Garovic, the objective has been to pinpoint the relevant chemicals or molecules.

Researchers have observed for many years that placentas delivered from preeclamptic pregnancies frequently showed indications of ageing more quickly than placentas delivered from normal pregnancies.

"However, it was counterintuitive to say that pre-eclampsia was a disease of ageing if you're looking at somebody who's 25 years old," Dr Garovic said.

In fact, many of the molecules that were elevated in preeclamptic pregnancies were well-known markers of senescence, a cellular state that literally means "the process of growing old."

Dr. Garovic theorized that senescence may be the pathway by which some women develop pre-eclampsia. Senescent cells stop dividing, but they do not die and are not always eliminated from the body. Instead, they sometimes accumulate in tissues and secrete harmful molecules.

Using samples and data from the Rochester Epidemiology Project, Dr Garovic has tracked various signs of ageing and senescence in women with and without preeclamptic pregnancies.

Together with Mayo Clinic obstetrician-gynaecologists Wendy White, MD, and Yvonne Butler Tobah, MD, she found that women who have had pre-eclampsia have a greater number of chronic conditions later in life—and develop these conditions at a much younger age—than those without a history of pre-eclampsia.

She also teamed up with Mayo Clinic cellular senescence experts James Kirkland, MD, PhD, and Tamara Tchkonia, PhD, to show that women with pre-eclampsia undergo accelerated ageing during pregnancy, as demonstrated by the "epigenetic clock."

These epigenetic clocks enable researchers to calculate the biological ageing of blood and other tissues by measuring the accumulation of methyl tags—which shift over time in any given organism—at hundreds of sites across the genome.

The researchers found that during their pregnancies and at the time of delivery, women with pre-eclampsia had aged an average of 2.4 years more quickly than women without pregnancy complications.

Dr Garovic holds out hope that new medications being developed in the field of senescence may one day prove to be safe for use during pregnancy, providing more options to women at risk.

Even if there are no specific treatments available right now to target senescent cells in women with a history of pre-eclampsia, Dr Garovic believes research on the associations between this pregnancy complication and future health issues will have a big impact.

Her studies and others are already leading to new guidelines for the screening and treatment of women at risk, with the ultimate goal of improving outcomes and saving lives.

For example, Dr Garovic served on a working group for the American Heart Association examining hypertension in pregnancy and penned the association’s scientific statement, which called for more work to protect women from complications of hypertensive pregnancies and possible post-pregnancy consequences.

"For women who have had pre-eclampsia, their blood pressure needs to be monitored, their cholesterol needs to be checked, their kidney function needs to be followed," she said.

"We need to keep track of their BMI and weight and try to manage lifestyle modifications and their health long-term."