Tally Health Files IPO Prospectus: Harvard-Backed Epigenetic Aging Platform Serving Over 270,000 Users

“Put simply, if you imagine DNA as a CD, over time that CD becomes scratched and can no longer produce the clear, pleasant sound it did when first released. As we age, our epigenome suffers similar damage, affecting cellular health and the way we age.” In an interview, Melanie Goldey, CEO of Tally Health, vividly illustrated the mechanisms underlying human aging.

Fortunately, relevant studies have shown that certain compounds and lifestyle interventions can slow the rate of cellular aging, and that epigenetic age can be measured accurately and reproducibly.

Tally Health is precisely such a company. Rooted in decades of research in epigenetics by David A. Sinclair, Professor of Genetics at Harvard University, it starts with DNA methylation testing to provide patients with “one-stop” anti-aging services. Tally Health’s offering comprises three components: the TallyAge test, a personalized action plan, and a unique blend of supplements developed by the Tally Health research team targeting hallmarks of aging. The service aims to help users take control of their aging process and reduce their epigenetic age.

Tally Health was co-founded by longevity expert and Harvard University genetics professor Dr. David A. Sinclair, along with serial entrepreneur Whitney Casey.

David A. Sinclair is a tenured professor in the Department of Genetics at Harvard Medical School, co-director of the Paul F. Glenn Center for Biology of Aging Research, and chair of the Academy for Health and Lifespan Research. He is renowned for his research on “why we age and how to slow the effects of aging.”

Meanwhile, Dr. Sinclair is the co-founder and co-editor-in-chief of the journal Aging. He holds more than 50 patents and has received over 35 awards and honors, including a fellowship from the American Federation for Aging Research, the Nathan Shock Award from the National Institutes of Health, the Junior and Senior Scholar Awards from the Ellison Medical Foundation, the Gairdner Biomedical Science Award, the Australian Medal for Medical Research, the Frontiers in Aging and Regeneration Award, recognition as one of Australia’s Top 100 Innovators, and inclusion in TIME magazine’s “50 Most Influential in Healthcare” and “TIME 100: The World’s Most Influential People.”

In 1995, he earned his Ph.D. in Molecular Genetics from the University of New South Wales in Sydney and conducted postdoctoral research at the Massachusetts Institute of Technology under Dr. Leonard Guarente, where they jointly elucidated the causes of yeast aging and the role of Sir2 in epigenetic changes induced by genomic instability. In 1999, he joined Harvard Medical School, where he has focused on the biology of aging and translational medicine for over two decades.

In the early stages, Dr. Sinclair’s research primarily focused on sirtuins, a class of protein-modifying enzymes that respond to changes in NAD+ levels and caloric restriction (CR). He also maintained strong interests in epigenetics, energy metabolism, mitochondria, learning and memory, neurodegenerative diseases, and cancer. The Sinclair Laboratory was the first to discover the role of NAD+ biosynthesis in regulating lifespan and the first to demonstrate that sirtuins are activated by CR in mammals.

Dr. Sinclair’s early academic explorations laid a robust scholarly foundation for Tally Health’s specialized anti-aging services, with the company’s TallyAge aging assessment method and anti-aging supplements deeply rooted in his scientific research achievements.

In 2019, Sinclair and his laboratory stated in "The Information Theory of Aging" that epigenetic changes causing cells to lose their identity are the primary cause of aging, and that this is a reversible process. This finding represents the culmination of Dr. Sinclair’s decades of research in epigenetics, elucidating the mechanisms of human aging and spurring the establishment of Tally Health.

Although various tests currently provide molecular-level insights into aging, the gold standard remains the measurement of DNA methylation. Methylation is a “tool” used by cells to control which parts of DNA are accessible or restricted. By adding a chemical group called a methyl group (-CH3) to specific DNA molecules, this region of DNA is marked, thereby influencing gene expression levels. DNA methylation patterns undergo dramatic changes over time, making them suitable for measuring physiological age.

In 2013, Steve Horvath, a biostatistician at the University of California, Los Angeles (UCLA), observed a correlation between DNA methylation and age: as individuals aged, methylation levels increased in certain genes while decreasing in others, resulting in a dynamic state. He therefore hypothesized that each age might correspond to a specific methylation profile.

Subsequently, leveraging gene-based “methylation” tags and applying machine learning to a large cohort of samples, Steve Horvath confirmed his hypothesis and developed the epigenetic clock. This clock estimates an organism’s physiological age based on genomic methylation profiles, achieving a measurement accuracy of over 98%.^[1]

TallyAge is an epigenetic clock based on DNA methylation testing, trained to predict users' biological age while incorporating variations in lifestyle factors (such as sleep, diet, exercise, and stress). It analyzes DNA methylation sites (CpG sites) and specifically selects those associated with aging.

This test is a simple, non-invasive saliva-based assay that can be performed at home. Upon registering for a Tally Health membership, users receive their first at-home TallyAge test kit, which measures biological aging and helps determine the starting point for their “anti-aging journey.” The TallyAge metric was developed using DNA methylation datasets from buccal cells of adults. For this quarterly aging assessment, users simply swab the inside of their cheek with a cotton swab, mail the test kit back, and leave the rest to Tally Health’s laboratory team.

Compared with other aging detection methods, TallyAge has many advantages. In terms of the testing method, blood collection is invasive and causes pain and discomfort to patients, while the TallyAge test uses buccal swabs, which are non-invasive and painless.

Furthermore, prior to launching its service, Tally Health’s research team spent one year curating a dataset based on samples from more than 8,000 highly diverse participants (aged 18–100 years, with over 30% being non-White). This dataset includes both single-time-point data and critical longitudinal data for each user. According to Tally Health’s official website, this unique collection represents the largest DNA methylation dataset derived from adult buccal swabs to date.

In terms of sample size, the TallyAge test boasts a large dataset with a balanced gender distribution and significant ethnic and racial diversity. In contrast, most other testing methods have sample sizes of fewer than 2,500, cover a narrower age range (typically excluding individuals over 90 years old), exhibit gender imbalances, and lack ethnic and racial diversity.

In terms of DNA methylation measurement technology, the TallyAge test is built using the modern MethylationEPIC array, capable of measuring approximately 850,000 DNA sites, whereas other detection methods rely on traditional arrays that capture only about 450,000 or 27,000 DNA sites. Finally, regarding the critical aspect of measurement accuracy, first-generation traditional models are trained to simply estimate chronological age and exhibit high test-retest error rates. In contrast, Tally Health employs a novel approach to train its next-generation models, which incorporate lifestyle and health factors and are optimized to maintain high reliability across repeated measurements.

Based on the TallyAge test results, Tally Health will provide an accurate analysis of users’ biological age, along with personalized recommendations to help improve aging-related conditions.

Tally Health provides personalized action plans based on members’ unique DNA profiles to improve their epigenetic age. These recommendations include increasing or decreasing the intake of certain food types, exercise, dietary management techniques, and alcohol consumption, among others. They are prioritized based on members’ DNA and lifestyle data to identify the factors with the greatest impact on aging.

Each recommendation and suggestion is supported by efficacy data from pioneering research. All recommendations and proposed protocols are accessible with a single click via Tally Health’s digital platform. Throughout the service process, the company continuously monitors patients’ conditions, enabling users to stay informed about their health status. Furthermore, users undergo retesting every three months to assess their progress and adjust their action plans accordingly.

To ensure the implementation of these personalized recommendations and enhance user adherence, Tally Health leverages a digital platform to help users cultivate healthy habits. Under the guidance of Tally Health’s digital platform, users will modify lifestyle factors that may accelerate aging.

Furthermore, Tally Health has developed two anti-aging supplements, Vitality and Amplify; the former targets the 12 identified hallmarks of aging, while the latter focuses on metabolism and mitochondrial health.

Vitality promotes optimal epigenetic function by enhancing key processes required for cellular repair and energy production. Its ingredients include calcium alpha-ketoglutarate, resveratrol, quercetin, fisetin, and spermidine, which have been shown in studies to promote longevity and health in small mammals. Additionally, this product is vegan, non-GMO, free from artificial colors, preservatives, endotoxins, gluten, and the nine major allergens.

Specifically, Vitality helps delay aging by inducing autophagy, providing a key mitochondrial metabolite for energy production, activating deacetylase proteins that regulate repair processes and modify the epigenome, and clearing senescent or “zombie” cells.

Amplify contains a potent blend of glycine, berberine, and phosphatidylcholine A. These ingredients have been collectively shown to enhance metabolic health, boost cellular energy, and improve mitochondrial function. Targeting established hallmarks of aging, the formula has been proven to extend lifespan and improve healthspan in complex model organisms.

Amplify activates the metabolic sensor and longevity enzyme AMPK; mimics the benefits of a low-calorie diet by clearing pro-aging amino acid methionine; enhances muscle function and exercise performance; and achieves anti-aging effects by increasing NAD+ levels through improved mitochondrial efficiency.

In terms of supplement quality, Tally Health maintains strict control, requiring all supplements to meet three standards: there must be multiple double-blind, randomized, placebo-controlled human clinical trials demonstrating that specific dosages are safe and well-tolerated; there must be robust mechanistic evidence showing that each molecule can mitigate established hallmarks of aging; and there must be peer-reviewed published data from small mammal studies indicating that each molecule can extend lifespan and/or increase healthspan.

In April 2023, Tally Health secured a $10 million seed funding round to scale its products and services. The round was led by Forerunner Ventures, with participation from L Catterton, G9 Ventures, and celebrity investors including John Legend, Chrissy Teigen, Pedro Pascal, Shonda Rhimes, Kevin Hart, Rich Roll, Whitney Cummings, and Zac Efron.

According to CEO Melanie Goldey, Tally Health attracted a waitlist of over 270,000 people prior to its official launch. Since its debut, the company has enrolled thousands of members and is experiencing exponential growth. Moving forward, Tally Health will continue to build a closed-loop system from aging detection to intervention, enabling broader access to the decades of longevity science expertise accumulated by its team.

Tally Health’s anti-aging services extend beyond merely measuring biological aging markers, enabling the development of personalized interventions and anti-aging supplements. This approach appears to bring the vision of resisting aging and extending lifespan closer to reality. However, it has also sparked related criticisms. For instance, the so-called “anti-aging intervention recommendations” seem little different from well-known health and wellness practices; mass-produced supplements with fixed formulations appear ill-suited to deliver truly individualized anti-aging solutions; some users have reported inaccurate test results; and questions remain as to whether the high cost of these supplements can ever achieve genuine “democratization of anti-aging.”

Currently, intense capital attention and a surge of users have propelled the anti-aging sector into the spotlight. However, beneath this fervor, it remains a topic worthy of reflection and scrutiny whether there is “speculative hype” and bandwagon entrants. In this field brimming with potential, whether Tally Health can truly create an “anti-aging miracle” still awaits verification and assessment by time.

References:

1. TimePie “Which Life-Extension Method Is Most Reliable? Epigenetic Clocks Can Tell You”