In 2020, amidst the hubbub of the pandemic, the world was rocked by a smaller (but perhaps more novel) story.
Claudette Cook, a 60-year-old woman from Alabama, gave birth for the first time to twin boys after starting fertility treatments just the year prior.
Though she thought she’d never have children, she was healthy and in good shape. So, when she met the love of her life, she decided it was time to dive right in.
Such late-life births are incredibly rare; past age 35, the chance of carrying a healthy, successful pregnancy drops off a cliff. But this story shows that there’s more beyond the uterine curtain – that it’s possible to maintain our reproductive longevity.
What is Reproductive Longevity?
Reproductive longevity is defined as the time between menarche and menopause. (Menarche is a woman’s first menstrual cycle, while menopause marks one year after the last.)
These markers are crucial for women, as they represent the breadth of their childbearing years. But there’s more to it than that: women who have longer reproductive longevity and later onset of menopause often live longer – as do their male siblings.
Currently, scientists believe the link between health and reproduction is due to the hormonal shifts that occur during menopause. As a woman’s hormones change, the effects ripple throughout the body and cause a host of age-related or aging-causing changes.
Still, the science is murky. All we know for sure is that in women, lifespan and healthspan increase as reproductive longevity increases. In the inverse, shorter spans of reproductive longevity are linked to women spending more of their life “medically frail”.
Reproductive Longevity: The Link to Fertility
Reproductive longevity and fertility are closely linked, but not exactly identical.
Generally, reproductive longevity is the age range during which a woman is said to be fertile. However, some 10-15% of women within childbearing years struggle to conceive, but still enjoy long, healthy lives, suggesting a disconnect.
Looking at Infertility
Clinically, infertility is defined as an inability to get pregnant after a year of unprotected sex. Women who suffer two or more failed pregnancies are also said to be infertile.
While rates of infertility vary between populations, around 15% of couples struggle to conceive after a year, and 10% within two years. The underlying cause of infertility can reside with the female, the male, or both.
By contrast, healthy couples under 30 have a 40% chance of conception within three months. According to the University of California San Francisco, these numbers decline with the prospective mother’s age.
Insightful Egg Counts
Another way to measure women’s fertility is by the number of eggs she carries at a given point.
According to the Buck Institute’s Center for Reproductive Longevity and Equality, female fetuses produce between 5-7 million eggs in utero. That number quickly dwindles: at birth, women have just 1 million. By the time puberty hits, the egg count has dropped to 500,000 or less.
Ultimately, by the time most women are ready to start a family, only 1% of the original egg count remains. By 37, women may have as few as 25,000 remaining; by 51, a mere 1,000.
Egg count isn’t the only metric that matters; egg health is crucial, too. Scientists have found that oocytes (female eggs) remain largely dormant until they’re needed or destroyed. Despite their dormancy, the older a woman gets, the more likely her eggs will suffer substantial chromosomal or DNA damage that impacts not just her fertility, but the health of potential offspring.
Differences Across Genders
Usually, the topic of reproductive longevity focuses on the female factor.
Studies show that a woman’s ovaries age faster than her other organs, becoming “geriatric” long before the rest of her body. That extends to pregnancies: any pregnancy after 35 is considered “advanced maternal age”. According to the Buck Institute, around 10% of otherwise-healthy women will become infertile at this point.
Though we know that it happens, scientists still aren’t sure why. Prevailing small-scale studies indicate that several molecular mechanisms contribute to ovarian aging, including:
- Oxidative DNA damage
- Impaired DNA repair
- Mitochondrial dysfunction
- And metabolic and energetic disorders
However, reproductive longevity isn’t just a consequence of female menopause.
Despite dying younger on average, men remain fertile for most, if not all, of their lives. In most populations, there’s no evidence of widespread mid- and late-life sterility. But in women, increased reproductive longevity leads to longer, healthier lifespans, suggesting the mechanism functions differently between the genders.
That said, the quality of men’s fertility may drop. Sperm counts often decrease, while genetic and epigenetic changes impair reproductive function. Often, as men reach their 50s and 60s, their ability to have children decreases mildly…and the children they do have are more likely to have genetic abnormalities, childhood cancers, and mental disorders.
The Link Between Reproductive Longevity and Aging
Most studies show that, though the average length of a woman’s life is increasing, reproductive longevity isn’t rising with it.
With children born today predicted to live to 90 or older, just 1/2 to 1/3 of every woman’s life will be spent in childbearing years. That even though women who naturally conceive after 45 often see their increased reproductive longevity reward them with longer, healthier lives.
Two Clocks, One Body
Unusually, human women have two separate biological clocks that tick at different paces.
The first is located throughout the majority of her body, from head to toe.
The second is in her ovaries.
While we don’t understand the mechanism, we do know that a woman’s ovaries age up to five times faster than the rest of her body. When the clock ticks past a certain point, the ovaries stop producing as much estrogen, throwing the body into menopause as it switches from a reproductive state to one of increased frailty and age-related diseases.
This switch comes with a cascade of negative health impacts that may contribute to the driving force of increased aging after menopause. When estrogen production stops, a woman’s bones, brain, cardiovascular system, and immune function take a hit, putting her at increased risk of:
- Heart disease
- Weight gain
- Dementia, including Alzheimer’s
What Factors Impact Reproductive Longevity?
Determining what contributes to increased or decreased reproductive longevity is no easy task. However, scientists have pinpointed several factors that affect both the age of menarche and menopause, which may yield clues.
More than a dozen factors are known to increase or decrease the age of menarche, including:
- Environmental conditions
- Geographic location and socioeconomic condition
- Parent and child’s nutrition and health status
- Parental education, occupation, and life expectancy
- Physical activity
- Family size
- Abuse or physical stress
- Nicotine and caffeine consumption
On the other end of the longevity spectrum, scientists have noted a range of influences on the age of menopause:
- The mother’s age of onset
- Age of menarche
- Gestational or ovarian age
- Use of oral contraceptives, alcohol, and tobacco
- Physical activity and body mass index
- A history of irregular menstrual cycles
- Number of past pregnancies
- Lead levels
- Education and socioeconomic status
One study in particular found that reproductive longevity can be influenced by as many as 290 genetic determinants. (Though it’s highly plausible that’s just the tip of the iceberg.)
In men, many of these same factors – like obesity, lead levels, and parental health – can influence reproductive longevity in old age. Lack of exercise and age-related comorbidities are also likely contributors.
How is Reproductive Health Determined?
Infertility doesn’t always mean a person’s reproductive longevity is low. Instead, it may indicate that during a person’s reproductive years, they simply can’t get pregnant with no impact on lifespan. And in many cases, treatments like IVF or hormone therapy can increase a person’s naturally poor reproductive health and potentially lead to better lifelong outcomes.
However, the links aren’t well understood – which may make determining reproductive health essential for your overall health.
To determine reproductive health and fertility, doctors can perform several tests. These may include:
- Blood tests to check for low thyroid function or egg supply
- Semen tests to check sperm count and motility (movement)
- Imaging tests to locate potential physical abnormalities or low organ function
These tests all look for markers of positive or negative reproductive health. Ovulation problems, hormonal imbalances, blocked fallopian tubes, or diseases like endometriosis or uterine fibroids all mark low reproductive health in women. These can also translate to lower lifespans or healthspans (though hormone treatments or surgery can sometimes correct imbalances).
What Can We Do to Maintain Reproductive Health?
According to UCSF, pinpointing the mechanism behind ovarian aging could help women carry healthy eggs for longer and increase reproductive longevity.
Currently, scientists believe that the cellular mechanisms that underlie general aging also control ovarian aging, perhaps by alternative or accelerated pathways. Targeting the cause of ovarian aging could potentially increase reproductive longevity, overall health, and the development of age-related diseases.
However, that’s easier said than done. Earlier studies point to a rare few mechanisms that could delay the onset of menopause or increase ovarian function. In lab studies, these include:
- mTOR inhibitors, which may reduce the depletion of ovarian reserves
- Sirtuins, which could boost the chromosomal integrity of ovarian cells
- Metformin, which may increase ovarian reserves
- Resveratrol, which could increase oocyte quality in older animals
However, women may have a couple home remedies in their back pockets, too.
The first is intermittent fasting and/or a healthy diet. Calorie restriction has been shown to increase the level of hormones and proteins that may preserve reproductive potential. Similarly, a healthy diet with limited processed foods and sugars could lead to better long-term outcomes.
The second is a small daily dose of melatonin. Though this neurotransmitter is most famous for promoting a good night’s sleep, it’s also thought to play a role in egg maturation and mitigating oxidative stress that contributes to ovarian aging. Some studies have shown that melatonin can protect oocytes during IVF, improve fertilization rates, and improve hormone function.
Reproductive Longevity: A Complex Mystery Not Without Hope
Reproductive longevity is a complex, little-understood topic. While we have a grasp on many of the what’s, we’re still working on figuring out the why’s.
What we do know is this: the longer women can hold onto their reproductive longevity, the healthier and happier they may be.
Even if you don’t aspire to have children at 60, getting plenty of exercise, eating healthy foods, and enjoying a good night’s sleep could all promote a longer lifespan in more ways than one.