Commentary: How women could be the key to unlocking longer life

PROVIDENCE, Rhode Island: For every man older than 110, there are nine women. Before she died in August at age 117,  supercentenarian Maria Branyas – the world’s oldest verified person – credited her bonus years not to any high-tech interventions but to eating lots of plain yogurt.

Her successor is also a woman, 116-year-old Ethel Catherman. And the record for longevity is held by another woman, Jean Calment, who lived to see her 122nd birthday.

Scientists still don’t fully understand why women live longer than men. The ageing process differs between the sexes, and in most mammals, females tend to live longer than males. Understanding the roots of these biological differences could help researchers better understand ageing in both men and women – and perhaps even reveal new clues to slowing it down.

For example, it remains unclear why women who undergo menopause later in life tend to live longer – and stay healthier. The answer isn’t just relevant to women’s health: A man’s longevity also appears to correlate with the age at which his sisters undergo menopause.

Scientists likewise don’t fully understand why women worldwide live, on average, a few years longer than men, yet are more likely to suffer from debilitating conditions such as arthritis and Alzheimer’s disease.

What researchers do know is that the human ovary follows its own clock and, unlike other organs, begins to age early. When women are still relatively young – in their late 30s and 40s – their ovaries undergo rapid ageing, with cellular damage comparable to that in other organs decades later, in our 60s, 70s and 80s.

HUGE DIFFERENCES BASED ON SEX

And yet, until relatively recently, research on ageing – like most medical research – was traditionally focused on males.  Male humans and even male lab animals were long thought to be equivalent to females, just without the “complications” of fluctuating hormones or pregnancy.

That bias began to shift in the 1990s when researchers started enrolling more women in clinical trials. Then, over the last decade, several new initiatives prompted the National Institutes of Health to require the use of more female lab animals and female cells in research.

“And surprise – it turned out there’s a huge difference based on sex, no matter what you do,” said Yousin Suh, a professor of reproductive sciences at Columbia University.

Pushing for the inclusion of female animals and humans has not only made medical research fairer to women, but it has also given scientists new insights into how the body works, insights that may be lost on the current administration, which is cancelling research it deems connected to diversity initiatives.

That’s unfortunate for everyone – women and men alike. Suh is leading a study using the human ovary as a test case for anti-ageing drugs. Scientists have had considerable success slowing ageing in mice, but those same techniques have not translated to humans. Ovaries may offer a better model because they consist of human cells programmed to age faster than those in other organs.

Suh’s earlier research showed that ovarian cells undergo the same ageing-related steps as the rest of our bodies: DNA accumulates mutations; the “epigenetic” system that activates and silences genes becomes scrambled; cellular “power plants” known as mitochondria lose function; and stem cells lose their ability to regenerate tissue.

She’s currently co-leader of a clinical trial enrolling young and middle-aged women to investigate the effects of a potential anti-ageing drug called rapamycin. The drug, derived initially from soil collected on Rapa Nui (Easter Island), is currently approved to suppress immunity and prevent rejection of transplanted organs.

Multiple studies have shown that rapamycin can dramatically slow ageing in mice, and while some researchers suspect it could extend the human lifespan too, proving it would take decades, given how long humans live.

A faster timescale is one big advantage of studying human ovaries. Researchers are monitoring the effects of rapamycin on various markers of ovarian health, ageing and fertility, Suh said, noting that any improvements in fertility could reflect broader anti-ageing effects.

WE’RE ONLY BEGINNING TO UNDERSTAND AGEING

Other lines of research are exploring why women, on average, live about five years longer than men. A 2020 study found that in animals with sex chromosomes, the sex with a matching pair – such as our XX – lived about 18 per cent longer on average than those with mismatched chromosomes, such as our XY. 

A study published last month in Science Advances reported that females have a higher life expectancy across most mammalian species. In contrast, males have a longevity advantage in most bird species, where they carry matching ZZ chromosomes and females have mismatched WZ pairs.

Another driver of sex differences in ageing is the force of sexual selection – the evolution of traits that boost reproductive success, sometimes at the cost of survival. Males might die earlier, for example, if they’ve sunk lots of energy into developing physical traits for display or combat against rivals – such as bright coloration, large horns or antlers, or greater body size.

And then there’s the mystery of menopause – a rare phenomenon in the animal world. Most female animals remain fertile until they are nearing the end of their lives, while only humans and a few marine mammals experience an extended healthy post-fertile phase. In some whale species, males die around the same age that females reach menopause – yet the females go on to live almost twice as long.

For all the centuries that people have yearned to live longer, we’ve only just begun to understand why and how we age. Scientists still don’t know why nobody – male or female – lives beyond about 120 years, or what it will take to surpass that apparent barrier.

However, maintaining better physical and cognitive health as we get older looks both achievable and imperative with an ageing world population. Only through more targeted and sustained research will we discover how to do that – whether with anti-ageing drugs or even advanced probiotic formulations of something as simple as plain yogurt.

The Trump administration’s war on diversity and inclusion in science rests on the notion that helping or studying some groups necessarily puts others at a disadvantage. That logic falls apart in biology, where diversity is fundamental to how life evolves and thrives – and ignoring it isn’t good for anyone.