Why Women Live Longer Than Men

HOST: In virtually every society in the world today, there is a group of people who live longer than everybody else, by an average of seven years. 

[THEME SONG IN]

It's not because they take special drugs or get experimental treatments. And it’s not because they live in a magical place where everybody drinks red wine and walks instead of driving a car. 

This group lives longer because of a trait they all share. and there’s about a 50 percent chance that you have it too.

That trait is being female. 

Across the world, women outlive their male counterparts. In some countries, like Nigeria, the difference is only about two years. In Russia, it’s more than ten years. On average in the US, women live to be just over 80, men just under 75.

And it’s not that there are an extra couple of years tacked on to the end of women's lives. Females have a lower death rate than men at just about every stage of life. During COVID in the United States, more men than women died of the disease in almost every age group. 

What explains this gap? Scientists are still figuring out the answer. 

Behavior has something to do with it. Women tend to go to the doctor more than men. They drive more carefully. They smoke less.

But behavior alone doesn’t explain such a widespread phenomenon. In recent years, scientists have learned that female aging is profoundly different than male aging – at every stage of life, and down to the very molecules of our cells.

I'm Carl Zimmer. And in this episode of The World As You’ll kKnow It, we’re talking to three experts about some groundbreaking new findings about female aging. And what these insights could mean – not just for women, but for all of us. 

[THEME OUT]

HOST: The fact that women outlive men is no secret: but it is a mystery.

Virginia Zarulli: This is something also that catches the attention. The first time you see this and you start wondering why, what is this, what are the reasons.

HOST: Dr. Virginia Zarulli is a professor of demography at the University of Padova, in Italy. She's been interested in this longevity gap since she was a student. And several years ago, she set out to see just how pervasive it is. Was there only a gap under ordinary circumstances? Or do women live longer than men even in extreme conditions?

Zarulli searched for populations who endured the most extreme conditions in history, like slavery, epidemics and famines.

One of the populations  she studied was on the western coast of Africa, in what is now Liberia. In the 1800s, several thousand African-Americans, both freeborn and formerly enslaved, arrived there on ships from the United States as part of a resettlement plan. But once the voyagers made land, they faced an unexpectedly harsh reality. 

Virginia Zarulli: These were people who were born in the United States. So when they moved to Liberia, they faced a completely different epidemiological environment compared to the one they grew up in.

Carl Zimmer: What does it mean to face a different epidemiological environment?

Virginia Zarulli: You are born in a place and in this place, there are all sorts of viruses and bacteria circulating and that's what you encounter and you grow up with and you develop immunity against these viruses. Then you move to a completely different environment and your immune system is not ready for that. Indeed, these people moving there faced what we call a mortality shock- 43, 44 % of them died in the first year. This is a crazy high mortality rate, like almost half of them. As of today, to my knowledge, it’s probably the highest mortality ever recorded in human history.

[MUSIC IN]

HOST: The suffering behind the statistics is almost beyond our imagination. People died at a staggering rate. But when you look at the sex divide…

Virginia Zarulli: It was very high mortality for both sexes, of course, but at all ages women were surviving a little better than men.

HOST: Women still outlived men. 

Virginia Zarulli: If you take the mortality rate of the people that these people are facing in the first year and you kind of freeze them in time and you apply them to a population, you obtain a life expectancy of 1.68 years for men and 2.23 for women. 

Carl Zimmer: Wow.

Virginia Zarulli: The population would go extinct.

HOST: Of course, that doesn’t mean that no one lived past the age of 3 – there were survivors. But the effect on average life expectancy shows just how severe the conditions were. 

[MUSIC OUT]

For another case study, Zarulli turned her attention to Iceland. In the nineteenth century, it suffered two terrible measles epidemics.

Virginia Zarulli: Measles was not endemic, which means it didn't steadily, constantly circulate in the population. I think it's interesting to know how the virus arrived, because at that time Iceland was a closed population, they didn't really have frequent contacts with the continent, with Europe. 

You know, at that time it wasn't easy to travel to Iceland. So it wasn't easy for Icelandic people to receive mail. they would receive mail maybe a couple of times a year in late spring and late summer. It was due to a Danish postal boat. In those two years it brought measles.

Life expectancy of Iceland dropped from, let's say, for males from 35 years of age before the epidemics to, like 18, and for females from 41 to 19.

HOST: As Zarulli looked at one disaster after another, she found that women consistently survived better than men. 

But perhaps what surprised Zarulli the most was that the biggest gap in survival rates wasn’t among adults. 

Virginia Zarulli: The biggest chunk of the total gap in life expectancy, was due to better baby girl survival than baby boys. So at infant ages, in the ages between zero and one. So the newborns, baby girls, were surviving better than the baby boys. And this is striking.

Carl Zimmer: Why do you find that striking?

Virginia Zarulli: Because how many ages there are, I mean, a person lives through many ages and yet one single age, only zero one, contributes to almost all the gender gap in such an extreme harsh condition. 

Carl Zimmer: So if you compared, say, adult women in their 20s to adult men in their 20s, the gap between them was much smaller.

Virginia Zarulli: Yes, still women had a lower mortality than men, but the gap was much smaller. I would like to add that in all these seven populations, we found that the biggest contribution to the gender gap, total gender gap in life expectancy came from the infant ages. 

HOST: And what struck Zarulli was that this is the one age where she expected males to have the advantage. 

In many cultures, boys have historically been preferred over girls. So she expected that boys would have a higher survival rate.

Behavioral differences between boy and girl infants are minimal, if non-existent. There could be different treatments of the adult towards the children, but in that case, even though we didn't have the data to check for this, in that case it's more likely that it would be in favor of boys rather than girls.

Virginia Zarulli: So we know that, for instance, where resources were getting scarce, when there was not enough food, they were probably prioritizing boys.

Carl Zimmer: And even in the face of that kind of discrimination, females still would end up with this lower mortality rate even in times of crisis.

Virginia Zarulli: Yes.

HOST: This led Zarulli to a much broader insight about women’s longevity. It doesn’t seem to be just a function of social conditions or behavior. Something must be happening on a much deeper level.

Virginia Zarulli: The fact that we found that most of the survival advantage of women under these extreme conditions came from a better survival of baby girls compared to baby boys points at some biological route.

[MUSIC IN]

HOST: As Zarulli analyzed historical records of births and deaths, she could see hints of something biological driving the longevity gap.

And biologists have started to look inside our cells to find out what exactly that might be. 

Dubal: There are certainly cultural, behavioral, environmental aspects to why women do live longer than men. But given how extensive and pervasive this is and the fact that we see this in the animal kingdom, that female animals across the kingdom in many species will tend to live longer than the male animals. It tells us there's something biological going on, that there's some component of genetics or hormones that are contributing to the female longevity.

HOST: Dr. Dena Dubal is a professor of neurology at the University of California, San Francisco. When she was a kid, she noticed that her female relatives lived a lot longer than her male ones. 

After she became a scientist, she decided to search for the reason behind that difference. She started by looking at our chromosomes. Could those strands of DNA explain the mystery?

Dena Dubal: It's a really remarkable and basic difference between the sexes that males, and we're speaking of mammals, including humans, males will have one X, and it comes from their mom, and one Y chromosome, which comes from their dad. And that is very different than females who will have two X chromosomes, one inherited from mom and one inherited from dad. And so there's a very basic genetic difference.

HOST: A quick note that we’re using the terms male, female, woman and man in this episode for the sake of simplicity. But those don’t fully represent the many variations that exist within sex and gender.

The x chromosome carries over 900 genes. Males have one x chromosome, which they get from their mother. And so they carry just one copy of each of those genes. Females have two copies, one from their mother, and the other from their father. Could that difference help women live longer than men?

In a study Dubal published in 2018, she and her colleagues used an ingenious method to isolate the effects of the x chromosomes on longevity. They manipulated the genes of mice, essentially mixing and matching their chromosomes and gonads - in other words ovaries or testes. They ended up with four types of mice.

XX with ovaries.

Dena Dubal: Those are typical females. 

HOST: XY, with testes – in other words, typical male mice. 

But then they engineered mice with two x’s  – like a female – but with testes like a male.

Dena Dubal: They develop as males. They are indistinguishable from XY males. They have male genitalia, testosterone, they fight in cages. They’re male mice.

HOST: And the fourth and final set of mice were xy with ovaries. 

Dena Dubal: These are female mice who have a uterus, a vagina. They cycle. They have estrogen and progesterone. But their genetics are XY.

HOST: And then Dubal and her team just… watched them age. 

Dena Dubal: It wasn't complicated. It was pretty straightforward. It turns out that in many strains of mice, female mice will live longer than the male mice. But what we found is that the mice that had sex XX chromosomes, regardless of growing up as male or female, lived longer than the mice with XY chromosomes. 

MUSIC IN

Dena Dubal: So it didn't matter a whole lot whether the organism had ovaries or testes, there was a strong statistical effect of having two X chromosomes in causing the longevity.

HOST: Double x mice outlived xy mice. It didn’t matter if they carried ovaries or testes. The x chromosomes extended their lives either way.

Carl Zimmer: So you're really able to zero in and say, there's something about chromosomes that really matters to this question about aging.

Dena Dubal: Yes, we were able to discern and dissect out the effect of having two X chromosomes and not to say that there weren't effects of gonads. There were effects of gonads. In fact, the longest lived mice were the combination of ovaries and XX chromosomes. So there's certainly a contribution of gonads, but for the first time we were able to really appreciate, discern and show that XX chromosomes contribute to lifespan using this very unique puzzle in mice.

Carl Zimmer: Were you able to look at the mice and maybe get any clues about what it is about that second chromosome that is making the difference?

Dena Dubal: That is the key question. What is it about that second X that is helpful? 

[MUSIC POST AND OUT]

HOST: No one knows for sure. But Dubal and other scientists have a couple ideas.

One idea comes from a strange fact that scientists have known for decades. Each cell in a female’s body carries two x chromosomes. But only one of those chromosomes is active. The other one is silenced. That means the cell can’t make proteins from its genes. 

This silencing happens early in the development of a female embryo.

Dena Dubal: And so in reality, even though females will have two Xs, each cell in the female body will only show one X and it'll either be mom's X or it'll be dad's X and it'll be completely random from cell to cell whether that cell shows mom's X or dad's X and that's very different than a male cell which will only show mom's X.

HOST: The female body is a mosaic of cells. in half of the cells, the mother’s x chromosome is active. In the other half, the father’s x is the one that makes proteins. And those cells are all mixed together: in the blood, in the muscles, in the brain.

It's a drastically different situation in a male’s body. Every cell looks the same. It has one x chromosome – with its 900 genes – and one y chromosome – with its 63 genes.

In a female body, half the cells use the 900 genes on the x chromosome from mom, and the other half use the 900 genes from dad. And many of those x chromosome genes are different from one parent to the other. Overall, females can make a much bigger diversity of proteins thanks to their x chromosomes.

Dubal speculates that this might help extend the lives of females.

Dena Dubal: That sort of genetic diversity might help to buffer the stresses of aging, when things go wrong biologically with cell signaling, with biochemical processes, maybe a female organism can buffer those problems with the different ways to address when things go wrong.

[MUSIC]

HOST: Dubal says, that’s not the only role that the x chromosome may have in aging. 

In March of 2025, Dubal and her colleagues published a paper outlining a remarkable discovery they’d made about the silent x – one that could change our understanding of how brains age. 

They took a look at the x chromosomes in the brains of female mice that were at least 20 months old – that’d be about 65 years in humans. And they noticed that many cells had not one active x chromosome, but two. Some of the genes on the second x were making proteins, as well.

Carl Zimmer: So you have a female mouse that has been going on with its life and now it's a ripe old age of two years old. And now you have these neurons that have been keeping one X chromosome silent since it was an embryo and suddenly now both X chromosomes are active.

Dena Dubal: Aging is waking up that silent X. it's not silent anymore. It's not completely activated, but it's not staying silent. So there is a percentage of the X that's waking up.

[MUSIC UP AND OUT]

HOST: Dubal and her team took a closer look at what happened to the mice when the silent x chromosomes woke up in their brains. One of the genes on the x chromosome is called plp-1. It makes a component of myelin. 

We talked about myelin back in our episode about how adults learn. It's the coating on neurons that acts like insulation, allowing information to move quickly through our brains. As we age, our myelin gets damaged, slowing down our cognition.

So here were old female mice making an extra supply of plp-1 in their brains. Dubal ran an experiment to see what that did for the animals.

Dena Dubal: We increased PLP-1 in the learning and memory center of old male mice and of old female mice. And quite remarkably increasing PLP-1 in a small number of cells dramatically improved their cognition, their learning and memory. Even when it was done in old age, which just tells you how changeable our brains are in aging and how this X factor could make a big difference. And not just in a female brain, but in a male brain too.

[MUSIC IN]

Carl Zimmer: It's such a textbook fact that females have one X chromosome silenced. It must have been quite a surprise to be finding these old mice with these second X chromosomes waking up.

Dena Dubal: It's a paradigm shift in how we think about the silent X for sure. And the implications for biology, for female-specific biology, for how we think about sex differences are really big. That silent X, matters in aging and particularly in brain health.

HOST: A single study on mice can only say so much about human aging. But Dubal’s team found another clue when they looked at brain samples donated by older men and women. The women’s brains had elevated levels of plp-1. maybe the silent x chromosome was waking up in their brains, too.

[MUSIC IN]

HOST: It's exciting science, and it’s starting to demystify why being female is such an advantage for longevity. 

But there is a catch. For women, a longer life is not all good news.

As women get older, they have a higher risk than men of developing a host of chronic diseases – from osteoporosis to rheumatoid arthritis to Alzheimer's disease. It's a puzzle that women live so long and yet suffer more health problems. Scientists call this the sex frailty paradox. 

One factor behind the paradox might be hormones – in particular, sex hormones, like estrogen and testosterone. They steer us through puberty and control the production of eggs and sperm. But they do other things, too. 

As it turns out, those hormones are pretty important to the immune system. And they have different effects in women and men.

[MUSIC OUT]

Lisa Mosconi: When our ancestors were roaming the earth, it was very effective for men to have a good amount of testosterone because it really supported an adrenaline response. It allows the immune system to mount a very strong acute response, which is important when you're wounded, when you're exposed to an infection, which is more likely to happen if you're a hunter. 

HOST: Dr. Lisa Mosconi is the director of Weill Cornell's Alzheimer's prevention program, as well as a professor of neuroscience there. Her research focuses on women’s brain health.

Lisa Mosconi: For women, it's more advantageous in some way to go slow and steady, right? In part, because we need to give birth. So our bodies are very much attuned towards protecting women and making sure that we’re able to overcome and survive childbirth.

HOST: The hormones that women produce may be one reason why they live longer than men. They prime the immune system to provide more protection against infectious diseases, ranging from covid to tuberculosis.

But when women go through menopause, their level of estrogen plummets. A bunch of changes follow. Women lose bone density, often leading to osteoporosis. Women also suffer from shifts in the immune system that can trigger inflammation, which can lead to things like arthritis.

Mosconi is investigating the connection between estrogen and Alzheimer's disease, which disproportionately affects women. And that’s not just because women live longer. Something else is going on. 

Lisa Mosconi:  There seems to be something about women that very specifically is linked to a higher risk of Alzheimer's. I'll tell you if it was just aging alone, then women would have a higher risk of all neurodegenerative disorders that are age related. Instead, it's only Alzheimer's disease and multiple sclerosis, which usually happens at a younger age. But the risk of disorders like vascular dementia, Parkinson's dementia, for instance, vascular dementia is 50-50, Parkinson's dementia, Parkinson's disease with dementia, the risk is higher in men. Right. And the other disorders are more evenly distributed. In fact, if you consider this- women who go through menopause in their 30s and 40s have a higher rate of developing Alzheimer's disease as compared to women who go through menopause in their 50s. 

Carl Zimmer:  And what does that tell you? 

Lisa Mosconi: It tells us that hormones play a big role in influencing neuroendocrine aging, which is the way that the brain ages together with their hormones.

HOST: Mosconi suspects that the drop in estrogen that comes with menopause can push some women down the path towards Alzheimer's.

Lisa Mosconi: When your estrogen levels are high, then the production of Alzheimer's plaques in the brain is low. So estrogen basically blocks the brain from forming these Alzheimer's plaques. So as long as estrogen is high, the brain is less likely to develop the pathology of Alzheimer's disease. When estrogen goes down after menopause, the brain is left without the strong layer of protection. And if you as a woman have a predisposition to Alzheimer's, that's when the predisposition can become measurable. It's like a tipping point for Alzheimer's risk. 

[MUSIC IN]

So just, I want to be absolutely clear, menopause does not cause Alzheimer's, it's a risk factor for Alzheimer's for some women. And this is one of the mechanisms by which some women's brains may be vulnerable to Alzheimer's starting in menopause.

HOST: If menopause is indeed a risk factor for Alzheimer's disease, then it might suggest a way to reduce that risk: by replacing the body’s disappearing hormones. 

Replacing hormones is not a new idea. Hormone replacement therapy is a menopause treatment that dates back to the ‘60s. It was used to ease symptoms like hot flashes and osteoporosis. but it became controversial in the 1990s, when studies showed that it could increase breast cancer risk. 

Mosconi doesn’t write off hormone replacement therapy. She says the studies about cancer risk were more nuanced than they were portrayed to be. and that some factors mitigated that risk, like which hormones were used, and whether the treatment was administered during menopause or long afterwards.

Mosconi says using hormone replacement therapy to prevent Alzheimer's is a compelling hypothesis. But more studies are needed to understand its potential. 

[MUSIC OUT]

Carl Zimmer: So what's the most important piece of data that you want to get to figure out how to use hormones to deal with these consequences of aging in women? 

Lisa Mosconi: I think the most compelling information would be a clear examination of whether hormone therapy taken in midlife can prevent the formation of Alzheimer's plaques and tangles in the brain. So see, this is the problem. The problem is that we don't have, at this point, level one, so -called level one evidence - clinical trial evidence that taking hormones in midlife can prevent Alzheimer's in old age. The reason we don't have it is that it's not possible to do such a trial. You can't start a treatment when a woman is in her late 40s, early 50s, and then keep her in the study for 20, 30 years until she develops Alzheimer's. 

Carl Zimmer: That's just too long. 

Lisa Mosconi: Yeah! It’s very hard to keep anyone in a study for like a couple of years. Imagine 20. We need a modern approach to this question. We need the same approach that we now use for Alzheimer's, which is this. We start treatment when people don't have dementia, but they may be at risk for dementia. Then we keep measuring them over time, showing a differential effect. So women who are not taking hormones, do they show an increase in Alzheimer's plaques and tangles relative to the women on hormones or not? That, to me, would be the ultimate proof that hormone therapy can reduce the risk of Alzheimer's.

HOST: Mosconi was recently appointed to lead a new program focused on women and Alzheimer's. It's funded by Welcome Leap, a charitable organization that supports scientific research with a goal of making major breakthroughs. She says one of her specific projects for the program is to create a way to test hormone levels in the brain.

Lisa Mosconi: Did you know that we cannot measure hormones in the brain? 

Carl Zimmer: Really? 

Lisa Mosconi: Yes. We can measure acetylcholine. We can measure serotonin. We can measure glutamate. We can now almost measure the GLP -1 compounds like Ozempic. You can kind of measure that inside the brain. We can measure inflammation. We can measure all sorts of stuff, but no hormones. So what we want to do is to develop the best possible way to measure hormone activity inside the brain. Why is that important? Well, number one, because we put women on hormones all the time, starting at puberty. And we have no clue what those hormones are doing inside your head. We just don't know. Globally, I think it's half a billion women on some form of hormone therapy right now, from birth control to endocrine therapy for breast cancer to menopause hormone therapy, medications for endometriosis or PCOS. We have no idea what any of these medications are doing inside your head. 

[MUSIC IN]

HOST: Like Dena Dubal, Mosconi’s drive to expand the knowledge of women’s health and aging is, in part, personal.

Lisa Mosconi: My grandmother, who was one of the brightest, most intelligent, strongest people I've ever met, she started showing signs of cognitive decline.

And later on, she developed Alzheimer's and died from it. And what was even more frightening is that my grandmother was one of four siblings, three sisters and one brother, and all three sisters developed Alzheimer's disease and passed away from it, whereas the brother did not. So that was terrifying, and heartbreaking and terrifying for my grandmother, for sure, for our family, for my mother, for myself.

And I started asking, does it matter if you're a woman when it comes to Alzheimer's disease? And people will say to me, well, we have known since the 1990s that after getting older, being a woman is the strongest risk factor for Alzheimer's disease. However, we're just going to let it go because Alzheimer's disease is a disease of old age and women live longer than men. So at the end of the day, it's just aging, it's just longevity and there's nothing more to it. And that to me as a woman and as a scientist just never really made a lot of sense. But my whole career has been really devoted to showing that that is not the best answer. There's a lot more to women and women's brains than aging alone. And today we recognize that that statement is profoundly incorrect. 

HOST: Mosconi says that, by 2050, more than 1.23 billion women around the world will be in or about to enter menopause. So figuring out the secrets of women’s aging – and the therapies that could help them lead healthier lives – could have an immediate impact on a huge number of people.

Dena Dubal believes that the benefits could extend even further. 

Dena Dubal: If we can understand what makes one sex more resilient in a certain measure compared to the other sex, and then we understand how and why, then we have new pathways and new molecules to then target for new therapies of resilience. And then we can apply that new knowledge, those new pathways, those new molecules, to both men and women.

[MUSIC OUT]

[CREDITS MUSIC IN]

HOST: On the next episode of The World As You’ll Know It:

Carl Zimmer: How much exercise should we aim for?

Eric Topol: There appears to be like a dose response, but still even limited exercise is helpful. You know, one minute of exercise is five minutes of healthy aging. That's a pretty good investment, 5X, right? Now, it might be a slight exaggeration, but you know what? There's something to that. 

Carl Zimmer: There’s a lot of talk also about whether we should be sitting or standing.

Eric Topol: I thought it was not real. But the more I got into it, it really makes a difference from the data that you're not sitting for undue periods.

Carl Zimmer: Can you talk a little about why something as simple as getting hearing aids might make a big difference with our brains?

Eric Topol: Yeah, there’s a hearing aid effect. Now why does that help to prevent Alzheimer’s? The likely explanation there is that auditory stimulation is important to keep that brain activated.

HOST: The World As You’ll Know It is brought to you by Aventine, a non-profit research institute creating and sharing work that explores how today’s decisions could affect the future. The views expressed don’t necessarily reflect those of Aventine, its employees or affiliates. 

For a transcript of the episode and more resources related to what you've just heard, please visit aventine dot org slash podcast. 

Danielle Mattoon is the Executive Director at Aventine. Bruce Headlam is the Editorial Director at Aventine.

Our Producer is Emerald O’Brien. Our Associate Producer is Marialexa Kavanaugh. 

Our Editor is Joel Lovell. Kamilah Kashanie is our Managing Producer. 

Original music by Davy Sumner with additional music from epidemic sound.

This episode was mixed by Marina Paiz.

Our head of sound and engineering is Raj Makhija. Our Senior Recording Engineers are Marina Paiz and Pedro Alvira. 

Fact Checking by Will Tavlin. 

Music licensing by Extreme Music and Epidemic Sound. 

Our executive producer is Asha Saluja. 

I'm your host, Carl Zimmer.

Make sure to listen to us on the Audacy app or wherever you get your podcasts.