Everything You Didn't Know About Reproductive Longevity
In a Nutshell
Dr. Jennifer Garrison outlines the Buck Institute's moonshot to end menopause by addressing ovarian aging, which accelerates twice as fast as the body, triggers cascading health declines (e.g., heart disease, cognitive impairment, osteoporosis), and correlates with overall lifespan—later menopause extends life for women and their male relatives. Women's eggs plummet from 7 million in utero to ~2% by age 40, driving menopause around 52; current fixes like IVF, egg freezing, and HRT are invasive band-aids, while underfunded research targets oocyte mitochondria, inflammation, and brain-ovary signaling for interventions like NMN. Join OVA membership at ovabuckinstitute.org to fund diagnostics, biomarkers, Evvatar models, and global efforts aiming to maintain 20s-like ovarian function lifelong, slashing $600B+ annual economic costs from menopause affecting 1B+ women by 2025.
These notes were generated by AI and may contain inaccuracies.
Welcome to June webinar on reproductive longevity with Dr. Jennifer Garrison from the Buck Institute for Research on Aging in the Bay Area, led by Dr. Eric Verdin. Buck Institute is the leading institution in longevity. Longevity Platinum trip run by Claire Adair featured work on women's reproductive longevity.
Dr. Garrison is faculty director of the Global Consortium for Female Reproductive Longevity and Equality, assistant professor at Buck, associate director of Buck-USC Biology of Aging PhD program, with secondary appointments at UCSF and Leonard Davis School of Gerontology at USC.
Buck launched moonshot to solve female reproductive aging. Aging is public health pandemic; age is number one risk factor for every disease of modern world. Biological age is malleable; aging can be slowed, stopped, or reversed. Modern medicine ignored age as therapeutic target until recent basic science discoveries.
Extending healthy longevity requires equality; interventions must be available to all. Without addressing reproductive longevity, gender inequality worsens. Women's reproductive span influences every aspect of life from puberty: health, family planning, career.
Menopause is literally the worst thing that can happen to a woman's body.
In healthy women, menopause triggers cascade of negative health effects: increased risk of cognitive decline, heart disease, stroke, depression, osteoporosis, arthritis.
Later menopause correlates with longer lifespan; brothers of women with later menopause also live longer. Bodies not designed to live past reproductive age 100,000 years ago; most died by 30.
Inclusive: "women" means anybody with ovaries. Ovaries are canary in coal mine for aging; age at twice the rate of rest of body. In late 20s/early 30s, ovaries geriatric.
Age at menopause correlates with overall lifespan; male relatives live longer too. Ovaries impact whole body via eggs and hormones.
Women have all eggs at 26 weeks in utero: 7 million. At birth: 1 million (sevenfold decline). Men produce 1000 sperm/hour lifelong. Decline to 300,000 at puberty (another third lost). By late 20s/30s: really low, ~5% original. At 40: 2%. Menopause when eggs run out, average age 52.
Don't understand what makes good egg or why numbers decline precipitously. Unknown causal factors/timers.
Precious few scientists at interface of reproductive aging; lack of funding for women's health. NIH required female inclusion in studies first time in 2014. Studies/drugs historically on men; women's cyclicity considered inconvenient noise.
IVF (43 years) and egg freezing are state-of-the-art band-aids; continue offering best options. Incremental progress; economically favorable to maintain status quo. Promises to women exceed understanding: don't know what makes good egg, how to freeze/revive properly.
For 1 viable egg post-freeze: need 15 oocytes to start (depends on age; 15 is a lot). Process barbaric/invasive.
Moonshot: understand ovarian aging causes, develop interventions to slow/reverse. Extend to 3% original eggs by 40 pushes menopause later, maintains hormonal balance/health longer (not for late babies).
HRT best treatment to stave off menopause symptoms (band-aid, state-of-the-art). Women's Health Initiative study (20+ years ago) wrongly claimed HRT causes breast cancer (not statistically significant, flawed).
Center for Female Reproductive Longevity and Equality at Buck Institute, seeded by BAKO Foundation. Building field: engage scientists, entrepreneurs. Global Consortium funds grants, builds ecosystem, industry-academia partnerships, accelerates lab-to-product (decades otherwise).
Promising targets: oocyte mitochondria (all body mitochondria from mom's egg), inflammation.
Eggs formed in utero: speaker's egg from grandmother's womb in 1956.
5-year: reframe diagnostics (primitive now, e.g., temperature); biomarkers/signatures of healthy reproductive aging.
Build translational advisory boards, hub facility at Buck Institute (architect Pei design).
Moonshot: get rid of menopause. Humans among ~5 mammal species with menopause; not biological imperative.
Goal: keep ovaries functioning for vitality/hormones like in 20s/30s lifelong (ovaries key but not only component).
Certainly ovaries are a key component, but they're not the only component. You need a functioning uterus. You need a lot of other things to have a baby.
For women in their 30s and 40s looking to maintain vitality, hormonal replacement at the right time is key. Hormone replacement therapy only works if the receptors for those hormones are still intact. When hormones go away, those receptors get downregulated. Starting hormone replacement therapy early is very important. There's a window of opportunity: somewhere between zero and six years after the onset of menopause. 10 years out, there wasn't as much benefit.
This is one of the most underfunded fields. Women should be outraged. There's a lack of public engagement, knowledge, and communication. Dr. Verda, David Sinclair, George Church, and others talk about age reversal. A lower step is helping women preserve ovary function longer. This has major knock-on effects for aging, the rest of the body, and men. It allows women to remain at highest function much longer.
Funding the Work
The Bako Foundation and Nicole Shanahan provided seed funding for the center and global consortium. They need to not be the only funders. Dramatic, huge work ahead.
50 million women in the US are going through or in menopause, increasing by 2.2 million every year. By 2025, globally over a billion women in menopause, more than 10% of the population. Negative health effects create health and economic burdens from decreased productivity. Vasomotor symptoms experienced by 80% of women: hot flashes, night sweats, brain fog affect quality of life, causing missed work. Lost productivity costs $150 billion per year. Increased healthcare costs above $600 billion a year. Economic burden is staggering.
OVA membership is $100 a year to engage the public, stay updated, and support the work. Email ovbuckinstitute.org or go to ovabuckinstitute1word.org. Buy as tribute to mom, sister, wife, girlfriend, or yourself. PhD Ventures and Abundance teams are buying memberships. Matching up to $50,000 of community memberships.
Evvatar is an ex vivo model to study menopause and reproductive decline. No great models exist; can't do many human experiments. Need model systems like cell culture or rodents. Best is human cells in a dish. Evvatar builds key features of ovaries in a closed cellular model to test therapeutics and see effects on all impacted tissues.
Investment Areas
- Novel model systems (e.g., ants for reproductive strategies)
- Novel targets
- Novel compounds or therapeutics Get smartest scientific minds to recognize the opportunity.
Niches needing innovation: Every aspect underfunded. Lowest hanging fruit: diagnostics, biomarkers. Need basic science on fundamental cues. Need data from large populations measuring hormones over time (current data is poor).
Entrepreneurs driving attention/funding: Build networks. Talk to early-stage entrepreneurs, VCs. Gather data creatively, low-cost, organically for ML analysis. Bring stakeholders together. Planning in-person summit in fall with biotech leaders, VCs, funders. Buck holding annual summit on women's reproductive health in May 2022.
Gynecologists advise ceasing HRT by 65 due to risks of blood clots, stroke, cancer. WHI study showed 1% increased breast cancer risk after 65, but weigh against bigger risks elsewhere (risk-reward balance, individual with doctor). Blood clots from oral HRT metabolized by liver increasing clotting factors. Use patch or cream instead.
Educate physicians with digestible state-of-the-art info and women with questions to ask doctors.
Ovaries age faster than any other part. Goal: understand fundamental drivers. First cue likely from brain (pituitary or hypothalamus). Ovaries influence health via hormones acting locally and signaling brain-reproductive tract (Wi-Fi communication). Understanding that chemical conversation key.
Preliminary rodent data (Dr. Verda/Franchesca Duncan): NMN and NAD metabolism positive impact on ovarian health, but dosing, translation to humans unknown. Promising.
Blood chemistry most common. Need large datasets across populations at different ages. Genetic background, environment interactions key. Ovarian aging influenced by microenvironment (inflammation), diet, overall health. Coming: wearables, implantables, consumables for continuous blood chemistry measurement feeding new models.
Contraceptives don't extend eggs. Woman loses ~1,000 eggs per cycle from puberty. Contraceptives prevent ovulating the one special egg but still lose ~1,000 (999 instead of 1,000), no difference.
Evolution: Don't fully understand why menopause evolved (evolutionary biologist in center studying, writing book). We don't need it. No downside.
Bodies not evolved past age 30; no selection against menopause, cancers, dementia post-reproduction.
Positives: Push back menopause age for better well-being/health: energy, cognitive clarity, bone density, arthritis prevention via brain-ovary hormone signaling. Issue of equality; impacts choices beyond fertility. Separates ovary as hormonal/energy system vs. reproductive organ. Beneficial for fertility too, giving control, freedom, choice.
Studies show benefit to number of biological children: more children, more positive longevity impact (cause or effect unknown).
Moonshots timeline (eliminating menopause, delaying puberty, extending fertility): 5-10 years: dramatic understanding improvements, therapeutics in preclinical/clinical
Preclinical and clinical studies are needed for compounds, and better understanding of biomarkers to tell a woman where she is in her reproductive span. On a longer timescale, attracting scientists to work on this problem and inducing funders to support this field in a big way will have no limits to accomplishments. This decade is magnificent in biology and medicine with convergence of CRISPR, gene therapy, AI, quantum computers, and quantum chemistry. Scientists focus where there is capital and greatest demands, so bringing capital and awareness drives the work. As a scientist, without funding, work cannot happen.
Consider joining at ovabuckinstitute.org as a member or to fund the work for massive impact.
The consortium is global, attracting scientists worldwide, while accounting for cultural norms on fertility, aging, and women's rights. Recently seated a new center in Singapore, with goals to seed innovation centers globally. Biology differs subtly by region; women in Asia have higher incidence of PCOS (polycystic ovarian syndrome). In Asia, discussions adapt; they do not do genetic testing before IVF. Advocating with NIH, NSF, and organizations like WHO for public funding. Successfully included reproductive aging in WHO materials to member states for the first time. Technology to uplift women's reproductive longevity will disseminate globally like women's rights over the past century.
Five other species undergo menopause, including four whales and orcas. Dina Amira, evolutionary biologist, is researching this. These species are not near each other on the evolutionary tree, no clear correlation with longevity or body size. Open questions; understanding this would help crack the problem.
For women in premature menopause due to ovary removal for chemotherapy, tumors, or cysts: consult a doctor. IVF was originally developed for women who had ovaries removed due to chemotherapy. Ovary removal presents health challenges; discuss with doctor.
To improve health span: get eight hours of sleep, remove sugar from diet, exercise every day (walk, swim). Mindset is critically important; neural circuits are malleable. No pill replaces diet, exercise, and sleep, which have profound impacts but are hardest due to fast-paced lives.
Personal routine: exercise regularly (run, yoga, mix it up for muscles), get enough sleep (previously chronically sleep-deprived), healthy mostly vegan diet.
Join OVA membership and support Buck Institute work. 50k matching grant supports OVA and Buck. Visit buckinstitute.org; Dr. Eric Verdin and team extend health span for women and men. Webinar will be available to share; tweet and retweet.
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