In a few short weeks, we will be launching one of our flagship longevity projects with the University of Copenhagen’s Center for Healthy Aging. Here, our Chief Scientific Officer, Tyler Golato, discusses why Molecule is doubling down on longevity.
The Importance of Longevity
Throughout human history, the idea of slowing down the aging process has captivated our imaginations and piqued our collective curiosities. There exists an enduring sentiment that the aging process is inescapable; like death, growing old is intrinsic and inseparable from life. Human progress in the realm of hygiene and medicine has led to expectations of leading a long life, and consequently, expectations of reaching an old age. However, until recently, becoming aged was a rarity; for most of our human existence, age itself was not a risk factor for death.
This changed with advancements in antibiotics and the ability to combat communicable diseases, which led to a more than 50% increase in human life expectancy since 1900. This rapid increase in human life expectancy over the past 100 years outpaces the increase in life expectancy from the previous 2000 years. For 99% of human history, the average life expectancy was between 25–30 years. However, living longer and growing older has had broad societal consequences. Today, age-related pathologies such as cancer, cardiovascular disease, and neurodegeneration are among the leading causes of mortality and disability. To combat this, we must achieve a greater understanding of the aging process, which mechanistically underpins all age-related diseases. A greater understanding underpinning the biology of aging will lead to broader therapeutic strategies to target the aging process itself.
The global elderly population is projected to substantially increase throughout the 21st century.
Therefore, interventions that ensure healthy aging are of critical importance. While recent decades have unearthed significant knowledge regarding the molecular basis of aging, interventions targeting aging are only just beginning to emerge.
To this end, several therapeutic regimens have shown exceptional promise in retarding aging in model organisms, and for the first time, this knowledge is beginning to be applied to human beings (de Cabo and Madeo, 2014). Whereas aging was once thought of as merely an unprogrammed series of largely random deleterious events, we have now identified genes and pathways that promote longevity. It is now known that specific cellular pathways likely underpin the aging process (Burgess, 2012). The field of biogerontology is undergoing a renaissance, with an explosion of interest and investment over the past decade.
The Emergence of a New Therapeutic Space
The longevity space itself has matured tremendously over the past 10 years. While we are finally beginning to understand the key factors that drive aging and are actively developing biomarkers that measure age, we still have a lot of work to do before there is a widely-available therapy that’s proven to increase lifespan. Some of the brightest minds in the field see these therapies on the horizon — SENS’ Dr. Aubrey de Grey believes one will be available within 20 years.
At this point, we know enough about the aging process to design new therapies that could have an unprecedented impact on aging. It’s now a routine procedure to reverse the aging of human cells in the laboratory dish.
The field of aging is growing fast — there are now over 100 companies dedicated to the research and product development in areas of senolytics, telomeres, stem cells, mitochondria, and gene editing. These are some of the core domains from which therapies that increase lifespan will emerge. You can learn more about many of the companies in the longevity space by checking out Karl Pfleger’s website, https://agingbiotech.info/companies/.
The development of a drug therapy that extends life is summarised by much of the ongoing work in senolytics, telomeres, stem cells, mitochondria, DNA damage and repair, and gene editing. At present, extending lifespan is a well-characterised theoretical case with some practical applications in model organisms such as fruit flies, roundworms, and mice. However, the leap to humans is a significant barrier. On the other hand, prospects have never been better. There are numerous global developments ongoing in the space with many well-funded companies and universities working towards using these techniques to treat disease, as well as slow-down or halt aging.
Clinical trials of drug therapies that extend life are difficult to launch due to aging’s characterisation as a non-pathological (not a disease). This is beginning to change, but at present, most drugs being studied for their effect on the aging process are being tested in clinical trials by targeting other indications. If a drug is being trialled to cure breast cancer, then, of course, it affects the recipient’s lifespan and could be classified as a longevity therapeutic. This represents the current divide between Longevity and Healthcare, and a barrier that we need to collectively overcome. Thus, the progress of drugs in clinical trials that treat aging as a disease is the core focus. Of the 120+ companies designated to developing Longevity therapies, 68 are pre-clinical, while only 3 are at Phase 3 clinical trials.
Indication expansion is the use of approved drugs in Longevity applications. Metformin and Rapamycin are the best known in this category.
Metformin is a medicine to treat type 2 diabetes and is being used in the 2020+ TAME trial to see if it does actually treat the diseases of aging; while the latter is a drug that prevents organ transplant rejection (and also slows Alzheimer’s in rats). Rituximab is a drug for the treatment of lymphomas, leukaemia, and some autoimmune disorders. Interestingly, through observation, doctors determined that if a stroke victim is on rituximab, their chance of having dementia is lower. Indication expansion is both fascinating, but risky in terms of prescribing a drug for a condition the patient doesn’t have. Many therapeutics are still at the animal study stage, but in general, this area shows the most near-term promise in generating viable pro-longevity therapeutics.
Molecule and Longevity
Molecule is interested in longevity research because of the broad promise it offers towards defeating age-related disease and helping us to live longer, healthier, and more robust lives. Most of the chronic diseases that pose the most significant threat to our mortality are age-related. Conditions like heart disease, diabetes, cancer, Alzheimer's, osteoporosis, and arthritis are largely responsible for the rapid decline humans tend to experience during the last 10–15 years of life. These diseases are responsible for the majority of costs experience by our global healthcare system. Longevity therapeutics offer the promise of preventing these diseases, and with it, the ability to age more gracefully and live like a young person, even in old age.
ARDD 2020: Addressing the challenges in drug discovery
At Molecule, we see longevity as an entirely new approach to medicine; one that has the potential to prevent, as opposed to treat or intervene. This approach will completely change the way the world approaches medical care and will have a profound impact on society. This also begs the question — who should control access to such vital therapeutics? Who should profit from them? Our core thesis relates to the democratisation and decentralisation of drug development, and most importantly, the democratisation of ownership. We are working to make the financing and ownership of longevity molecules public and democratic — we believe the cure for aging and the prevention of age-related disease should belong to all of us.
In a few short weeks, we will be launching one of our flagship longevity projects with one of the most brilliant minds in biogerontology. This project comes to us from the University of Copenhagen’s Center for Healthy Aging, and will focus on the creation of novel therapies to directly target the aging process. We will be coordinating the financing of this project, and distributing equity to parties and individuals interested in owning a part of the future of longevity therapeutics. We are extremely excited to support this project and help make the creation of therapeutics to combat aging a reality.
We will be working with some of the leading experts in the longevity space, and if successful, the project could generate multiple therapies to extend human life. This project is in the early pre-clinical stages, but we already have robust human data suggesting that these compounds extend human lifespan. We will be making an announcement with more details of the project soon. Stay tuned.
If you would like to learn more or get involved with the project, do not hesitate to reach out to us.
