For decades, conversations about female fertility have focused almost exclusively on timing: the “biological clock,” cliff at 35, and the rapid transition into menopause. All of these are real physiological considerations, but they are only part of a much larger story about cellular aging, energy decline, and metabolic resilience.
By popular request, we’re returning to one of our earliest posts on longevity, specifically geared toward women. Over the past few months, many readers have asked us to expand on the relationship between NAD+ and fertility decline with age. So in this week’s chapter, we’re taking a deeper look at what’s actually happening at the cellular level, and what it means for both fertility and long-term women's healthspan.
Why Egg Quality Declines With Age
Biologically, women are born with all the oocytes (eggs) they will ever have. Unlike many other cell types, oocytes do not continuously regenerate. Over time, their cellular machinery becomes more vulnerable to damage, and one contributor is the gradual decline of NAD+ (nicotinamide adenine dinucleotide).
NAD+ is a molecule that, not only oocytes, but every cell depends on for:
- Energy production, especially inside mitochondria (the “power stations” of your cells)
- DNA repair
- Stress responses
- Cell survival pathways
Think of it as one of the body’s fundamental “currency” molecules. Without sufficient NAD+, cells, including oocytes, lose the ability to maintain healthy structure, manage oxidative stress, and repair damage, leading to a gradual decline in egg quality over time.
Across tissues, NAD+ levels fall significantly with age. But in oocytes, this matters even more as they heavily rely on mitochondria.
Eggs contain more mitochondria than almost any other cell in the body. These mitochondria power the early stages of embryo development, long before an embryo implants and can draw energy from the maternal blood supply.
As NAD+ levels fall, either naturally with age or due to other biological complications, egg cells become more vulnerable to damage. Over time, this contributes to the well-known decline in egg quality, lowering fertility and increasing miscarriage or chromosomal-abnormality risk.
This decline doesn’t begin at menopause, it starts much earlier. In fact, noticeable decreases in oocyte quality can begin in the early 30s, although the effect becomes substantial after age 35, according to large population studies.
What Emerging Research Shows on NAD+ Precursors and Oocyte Health
In recent years, a growing number of studies, primarily in animals, have investigated whether boosting NAD+ levels can restore key aspects of oocyte function.
Two NAD+ precursors (molecules that serve as building blocks that cells use to produce NAD+), NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside), have been studied the most extensively. When researchers increase their availability, several changes happen inside aging oocytes, including:
1. Improved mitochondrial function in oocytes
In aged animal models, supplementation with NMN has been shown to:
- Increase NAD+ levels in ovarian tissue
- Reduce mitochondrial fragmentation
- Restore energy production within oocytes
Mitochondrial health is one of the strongest predictors of egg developmental potential.
2. Better chromosomal alignment and structure
Eggs need to divide their chromosomes evenly to develop normally. As eggs age, this process becomes less accurate. Animal studies show that boosting NAD+ helps support this division process, lowering the chance of chromosome mistakes, which is one of the main reasons why fertility drops with age.
3. Reduced oxidative stress and DNA damage
In bovine and mouse models, supplementation reduced reactive oxygen species (ROS) inside the oocyte and helped maintain DNA integrity. Oxidative stress is one of the main pathways through which aging harms egg quality.
4. Higher embryo development potential
Across several animal studies, eggs that received NAD+ precursors developed more normally. They were more likely to mature properly, become fertilised, and grow into healthier early embryos. Although this research is still preclinical, the pattern is consistent: raising NAD+ appears to help older eggs function more similarly to younger ones by supporting the cellular pathways that weaken with age.
But What About Humans?
This is where the conversation becomes more cautious, and where additional funding is critically needed.
Human data is promising but limited.
A small number of early-stage human investigations, some where researchers simply track what happens in people who are already taking NAD+ precursors, and others where small groups are given the supplement in controlled settings, have begun to explore these questions. But:
- We do not yet have large, randomised clinical trials.
- Optimal dosing is unclear.
- Safety during preconception and pregnancy is still being studied.
- We do not yet know whether the improvements observed in animals translate fully to humans.
In other words, the mechanistic rationale is strong, the preclinical data is compelling, but the clinical evidence is not yet mature enough for recommendations.
This is a familiar story in women’s health research: enormous potential, but historically low investment.
Why This Research Matters Beyond Fertility
It’s easy to think of egg quality as relevant only for conception. But oocyte health is a window into something much broader: the pace of female aging.
Here’s why:
1. Reproductive aging is one of the earliest aging processes in the human body.
Ovarian aging begins decades before visible signs of aging. It may be our earliest biomarker of overall biological decline.
This is a paradigm shift: instead of seeing fertility and longevity as separate topics, the science now shows they are deeply intertwined. If we can better understand, and eventually support, the cellular pathways that maintain oocyte quality, we may unlock new ways to extend healthy years for women as a whole.
2. Menopause marks a turning point in female healthspan.
The gradual loss of oocytes over many years is what eventually brings women to menopause, an event that marks the culmination of decades of ovarian aging rather than a sudden change. Menopause then becomes a major turning point in women’s healthspan, after which several health risks rise sharply.
- Cardiovascular disease
- Osteoporosis
- Metabolic decline
- Cognitive aging
- Depression and sleep disturbances
- Weight gain and loss of muscle mass
This healthspan drop is partly driven by estrogen decline, but also by changes in mitochondrial function and cellular energy pathways that NAD+ directly influences.
Where LSF Comes In: Funding the Missing Pieces
Despite the potential impact, research on female reproductive aging is vastly underfunded, especially compared to other areas of longevity science.
Most major funding bodies focus on late-life disease, not early-life cellular decline. Fertility research, meanwhile, is often limited to IVF-related outcomes rather than fundamental biology.
This leaves a significant gap with tremendous opportunity for impact:
Who is funding the science that explores how women age at the cellular level, and how we might slow or prevent that decline?
At the Longevity Science Foundation, this gap is exactly where we focus our efforts.
We look to support early-stage, high-impact research that traditional funding sources overlook. This includes the biology of ovarian aging, mitochondrial decline, and NAD+ pathways, areas that could transform both fertility care and women’s long-term health.
Our goal is to:
Extend healthy years for women by addressing the core biological drivers of reproductive aging.
If this is an area you care about, you can directly support research in this category. When donating, you can choose “Female Fertility & Longevity” and 100% of your contribution will go to research.
Donate here: https://longevity.foundation/support-us