People who lived through the Irish Potato Famine, enslavement in Trinidad and Icelandic measles epidemics all have something in common: Women outlive men in dire circumstances.
That's because the female body is built for resilience and longevity, as CNN found while conducting research for a new book, "The Stronger Sex."
Despite having more complex reproductive organs and the burdensome, sometimes fatal, functions that come with them — menstruation, pregnancy, childbirth and breastfeeding — female bodies tend to outlast male bodies.
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And that's the case even though girls in many parts of the world have access to fewer resources, such as food and medical care, than boys do.
That female toughness holds true in extreme circumstances, as Virginia Zarulli, now an associate professor of demography at Italy's University of Padua, found when she analyzed survival data across seven historical populations experiencing famines, epidemics and enslavement.
Under these brutal conditions, women outlived men across almost all ages and locations, including among the "high-mortality" populations who confronted famine in Ukraine, Ireland and Sweden; enslavement in Trinidad; and measles epidemics in Iceland, according to her 2018 study, published in the journal PNAS.
Even newborn girls in these environments had a higher survival rate than newborn boys — a hint that the female survival advantage is rooted in biology.
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Essential female strength also shows up today in places where women experience fewer extreme physical stresses overall: "When we analyze the empirical data, for modern people it shows that death rates for men are higher than for women, pretty much at every age," Zarulli said.
Recognizing and building on these sex-based differences can help transform how we approach health care, including treatments for cancer and vaccine protocols — making medicine more precise, personalized and effective, especially for women.
Female chromosomes and hormones
People assigned female at birth have two X chromosomes, a fundamental advantage over XY, the chromosomes males have at birth.
That's because the X chromosome is much larger, containing roughly 10 times more genes.
Female bodies therefore have access to a wider range of immune genes, making their defense system remarkably strong and diverse.
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As neurogeneticist and evolutionary biologist Dr. Sharon Moalem wrote in "The Better Half: On the Genetic Superiority of Women," his book about the XX chromosome advantage, "Women have immunologically evolved to out-mutate men."
Since viruses and bacteria are always mutating, an immune system that can quickly adapt is more resilient.
Estrogen, generally higher in female bodies, also confers a variety of immune advantages.
As a result, female mammals — including humans — have better-equipped immune systems, in both their innate, generalized responses and their adaptive, specialized responses.
Female bodies also have higher counts of active neutrophils, the most common type of white blood cell that fights infections.
Scientists have also found that female bodies have more robust B cell activity — the action of white blood cells that adapt to fight off viruses or bacteria.
This advantage may also be due in part to estrogen, and researchers are trying to tease apart what is mediated by hormones, what is affected by genes and what might be attributable to other causes.
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Women produce more targeted antibodies to fight infections and also retain immunological memory longer, making their bodies more adept at responding to future infections, according to researchers.
this all leads to "the very well-known phenomenon that males tend to be more susceptible to a lot of diseases than females — though not in every disease or every individual, of course," said Marlene Zuk, a Regents Professor and evolutionary biologist at the University of Minnesota in St. Paul.
Since female bodies mount stronger immune defenses, they generally have a stronger vaccine and virus response, a greater ability to fight off sepsis and a decreased risk of some cancers.
The downside of this powerful system, however, is that women get more autoimmune diseases than men do.
Women are also more likely to live with chronic illness after surviving diseases that would have killed male bodies.
The effect of testosterone
Testosterone also seems to be an immune disadvantage, and males have more of that hormone than females do.
Zuk said that in early experiments scientists found they could "neuter male animals and their immunity would get better or inject female animals with testosterone and their immunity would get worse."
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Why?
It may be that testosterone enables male animals toward greater reproductive success by "living hard and dying young," Zuk said.
Some of the female immune advantage may be male immune disadvantage, and while it's accepted that hormones affect immunity, determining to what degree is an ongoing research question.
Physiology and culture
Some scientists argue that lifestyle and culture lead to a significant part of the male longevity disadvantage.
As a population, men tend to smoke more, drink more alcohol and engage in riskier activities than women, and men tend to exclude most women from more physically dangerous jobs.
Studies focused on what happens when women adopt some of the unhealthy habits traditionally more likely among male populations, such as smoking, still show that women live longer than men, Zarulli said.
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"In populations where men and women had the same lifestyle, there was still a difference in mortality — women had a higher life expectancy than men."
The female advantage is likely due to more than genetic and hormonal factors, according to new research: It's also found in the very structure of women's bodies.
At North Carolina State University, a team led by microbial ecologist Erin McKenney and forensic anthropologist Amanda Hale conducted a landmark study measuring the lengths of the small intestines in cadavers for the first time since 1885.
The team discovered that women's small intestines were significantly longer than men's — an advantage that allows women to extract more nutrition from the same quantity of food.
This finding, published in the journal PeerJ in a 2023 paper, might be explained by the extra demands on female bodies throughout human history: "The vast majority of the nutrients you need to replenish your system — especially during reproduction and nursing, like protein and fat — that's what's being absorbed by your small intestine," Hale said.
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This could be a key piece of the "Female Buffering Hypothesis" — the idea that female biology evolved to withstand environmental and physiological stress better — according to Hale.
Traditional medical research has long ignored the complexities of the female body. As these genomic and physiological functions are better studied and understood, the drivers behind the strength and resilience of the female body will come into focus.
This knowledge will inform more targeted treatments for infection and immunity—for all bodies.
