Science

What is Spermidine?

Spermidine is a naturally-occurring and potent polyamine (a kind of protein) known for inducing autophagy, the body's cellular renewal and recycling process. It also inhibits 9 of the 12 Hallmarks of Aging, the paths down which we age.

2/3 of the spermidine found in the human body is produced endogenously, or in the body, by the gut microbiota and various tissues. The final 1/3 is found exogenously, or externally, in the food that we eat.

As we age, our body's ability to produce it declines. To restore youthful levels of spermidine, we have to look externally. Otherwise, our cells' ability to trigger autophagy will continue to decline and the aging pathways will progress.

Proven Spermidine Benefits

In addition to inducing autophagy, spermidine and its co-occurring precursor and successor, putrescine, and spermine, are associated with several essential cell functions and the maintenance of cell homeostasis. Polyamines are essential for cell growth and proliferation and tissue regeneration. They stabilize DNA and RNA, have antioxidative activities, modulate enzyme functions, and are required for the regulation of translation. They also help to control apoptosis (cell death) and play a role in learning and memory.

Supplementation with spermidine in humans has been shown to have a myriad of positive effects including, but not limited to, protecting brain and heart health, improving hair growth and fullness (including eyelashes), and strengthening nails.

According to a landmark paper and its recent update by Lopez-Otin et al, aging is driven by 12 “hallmarks”. Among them are mitochondrial dysfunction, stem cell exhaustion, disabled macroautophagy, and gut dysbiosis, which all are known to be ameliorated by spermidine supplementation. Spermidine is one of few known compounds thought to reduce or reverse the effects of multiple hallmarks; through its induction of autophagy, in particular, it is thought to impact as many as nine of the 12 hallmarks.

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Spermidine Targets 9 of the 12 Root Causes of Aging

Impaired autophagy

Have you ever thought about what would happen if you never took out the garbage? Rubbish would begin to pile up, decompose and generally get in the way of how things ran and looked in your home. This is exactly what happens inside your body if it can no longer trigger autophagy, which is your body's cell renewal and recycling process.

Mitochondrial dysfunction

As cells age, their mitochondria (the "cell powerhouse") lose the ability to provide cellular energy and start self-destructing by releasing harmful reactive oxygen species (ROS), creating oxidative stress. Being the energy source of the cell, you would feel mitochondrial dysfunction as low energy levels.

Stem cell dysfunction

Stem cells lose their ability to divide as we age, and we are therefore unable to replace cells that have migrated, differentiated, or died. As a result, we exhibit the outward features of aging, such as gray hair, fine lines, and wrinkles, and slower muscle and wound repair.

Inflammation

Heard the term “inflammaging”? It describes the gradual increase of inflammation as we age. Increased inflammation can lead to various diseases and is clearly linked to all other aging pathways both in its tendency to promote the other Hallmarks of Aging, and to result from them. It's a toxic cycle!

Telomere attrition

Telomeres are the end caps of our chromosomes, and their length determines the number of times a cell can divide. When the telomeres are dysfunctional, or unusually short, premature development of diseases and aging occurs. When the telomere length is long or maintained, cells can live longer.

Gut dysbiosis

70% of our immune system lives in the gut. Being located there, one of the immune system's responsibilities is to maintain bacterial balance in the gut microbiome. Since the immune system loses effectiveness with age, it is unable to perform its maintenance role in the gut and bacterial diversity suffers.

Epigenetic alterations

Your genome is like sheet music, and your epigenome is how that music is played. The sheet music is always the same, but we can influence how it is expressed. Without changing our lifestyle factors, epigenetic changes accumulate as we age.

Loss of proteostasis

AKA, poor protein folding. Proteins are responsible for nearly every task in our body, including cell shape, waste cleanup, inner cell organization, and routine maintenance. To function properly, proteins need to be folded perfectly.

Impaired intercellular communication

As cells age, they emit an increasing number of inflammatory signals, like "alarm bells", to alert the body that they need to be repaired. But when chronically sounded, these alarms can "inflammage" surrounding cells.

What is Autophagy?

Autophagy is a complex, tightly regulated, cell self-eating process. A leading University of Oxford scientist and member of our scientific advisory board, Professor Katja Simon, describes autophagy as, “the recycling van that delivers the rubbish to the recycling center. It is very important to degrade toxic waste for the survival of the cell, and a cell without autophagy cannot survive.” Beyond the degradation of waste, we have learned that autophagy plays crucial roles in differentiation and development, cellular and tissue homeostasis, protein and organelle quality control, metabolism, immunity, and protection against aging and a diverse array of diseases.

Ground-breaking science by Simon and others has made it clear that autophagy is a crucial process at the cellular level that benefits the entire body. It is no surprise, then, that Yoshinori Ohsumi, the Japanese scientist who discovered autophagy’s mechanism of action, won the Nobel Prize in Medicine or Physiology, in 2016, for his work. He was able to demonstrate that this process of cellular recycling and renewal plays a key role in human health and in preventing the diseases of aging. We are lucky enough to work with him via the Japan Autophagy Consortium, of which we are the only non-Japanese member!

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Benefits of Autophagy

Cardiovascular health

Cognition and memory

Immune function

Healthy joint function

Lifespan

Our Scientific Advisory Board

Professor Denis Noble

World-Renowned Physiologist & Emeritus Professor of Physiology, University of Oxford (Oxford)

Professor Denis Noble is a globally-recognized British biologist who developed the first mathematical model of cardiac cells in 1960. He held the Burdon Sanderson Chair of Cardiovascular Physiology at the University of Oxford from 1984 to 2004 and was then appointed Professor Emeritus and Co-Director of Computational Physiology.

On an international scale, he was elected President of the International Union of Physiological Sciences (IUPS) at its Congress in Kyoto in 2009, and then elected for a second term at the 2013 Congress in Birmingham, UK. As a pioneer in the field of systems biology, he is the author of the first popular book on Systems Biology, The Music of Life. His book, Dance to the Tune of Life, Biological Relativity, extends the systems approach to biology, including evolutionary biology. Denis Noble has published more than 600 papers and 11 books. Together with Leslie Kenny, Dr. Paul Ch'en and Sir Christopher Ball, he is a co-founder of the non-profit organization, Oxford Longevity Project.

Dr. Katja Simon

Oxford University Professor of Immunology & Head of the "Autophagy in the Immune System" laboratory, Max Delbruck Center (Berlin)

Dr. Katja Simon began her autophagy research as Professor of the Immunology at the Kennedy Institute for Rheumatology, University of Oxford. As a principal investigator, she set up an independent line of enquiry investigating autophagy, another cellular process determining cell fate, in the hemato-immune system. Her group discovered that autophagy, the main conserved cellular bulk degradation pathway, maintains healthy red blood cells, stem cells and memory T cells and promotes differentiation while preventing aging of the hematopoietic system. She has since been appointed to Head of the "Autophagy in the Immune System" laboratory at the Max Delbruch Center in Berlin as part of an initiative to attract outstanding female scientists from abroad. She and her team are continuing her research on autophagy in the immune system there.

Dr. Ghada Alsaleh

Principal Investigator in Immunology and Autophagy & Leader of the UK's First Space Innovation Lab, University of Oxford (Oxford)

Dr. Ghada Alsaleh moved to Oxford in 2017 to pursue her career as a scientist and to join Professor Katja Simon’s group at the University of Oxford's Kennedy Institute for Rheumatology, where she developed a growing curiosity about aging and the regulation of biological processes that are disturbed during the aging process. In her research, she showed that autophagy is specifically reduced in older human lymphoid cells, which contributes to compromised memory T and B cell responses in the elderly. This work has uncovered novel targets and biomarkers for the development of anti-aging drugs for human T cells.

Dr. Ghada was awarded funding for her proposal “Targeting autophagy for the treatment of osteoarthritis”. Osteoarthritis (OA) is the most common form of arthritis worldwide but lacks effective therapy. In this proposal, she aims to design a genetic screen using TFEB protein expression as a read-out to identify new potential targets for the treatment of Osteoarthritis and various age-related diseases. She has recently become leader of the UK's first Space Innovation Lab, which aims to understand the effect of space microgravity on the aging process.

Dr. Sasi Senga

Neurosurgical Oncologist, Lecturer in Medicine, Author & Researcher, University of Oxford (Oxford)

Dr. Sasi Senga is a neurosurgical oncologist with two Masters - one in Neuroscience and another in Cancer & Therapeutics - and specialist training from the Dana Farber Cancer Institute and the Barts Cancer Institute. He graduated as an Oxford Clarendon Scholar and Excellence Award/Top Honours Award recipient from Harvard Medical School. He also runs a cancer foundation for the underprivileged in two countries in memory of his mother, Kalavathi, who passed away to cancer, has authored a few books on cancer, and is currently working on a paper on the Hallmarks of Cancer.

Our Clinical Advisory Board

Dr. Paul Ch'en

Holistic Cancer Care Coach, CanSure Heal It, GP Partner & Doctor to Keble and Sommerville Colleges, University of Oxford (Oxford)

Dr. Paul Ch'en is a Practice Partner at the Observatory Medical Practice in Jericho, Oxford, where he is also the College Doctor to Keble and Somerville Colleges at the University of Oxford. Paul has recently embarked on a new chapter as a Holistic Cancer Care Coach through his online coaching service, CanSure Heal It. This service supports newly diagnosed cancer patients to take charge of their health and gives them the tools to help manage their condition. As a former cancer immunologist, he has a particular interest in the early diagnosis of cancer and is keenly interested in preventing the diseases of aging, cognitive behavioral therapy and acupuncture. Having had his early education in Japan, Dr. Ch'en also stays abreast of the latest Japanese therapies and research to promote healthy aging, reverse disease and live a long, healthy and happy life. He also co-founded the non-profit organization dedicated to educating the public on healthy aging, the Oxford Longevity Project, with Oxford Healthspan Founder, Leslie Kenny, Scientific Advisor, Professor Denis Noble, and Academic and Former Warden of Oxford University's Keble College, Sir Christopher Ball.

Dr. Sandra Kaufmann

"Best in Medicine" Longevity Doctor & Creator of the Kaufmann Anti-Aging Protocol (Miami)

Dr. Sandra Kaufmann began her academic career in the field of cellular biology, earning a Master’s Degree from the University of Connecticut in Tropical Ecology and Plant Physiology. Turning to medicine, she received her medical Degree from the University of Maryland, and completed a residency and fellowship at Johns Hopkins in the field of pediatric anesthesiology. Presently, she is the Chief of Pediatric Anesthesia for the Memorial Health Care system and the Joe DiMaggio Children’s Hospital in Florida and recently received the accolade of "Best in Medicine" from the American Health Council. She also practices as a longevity doctor and created the first-of-its-kind Kaufmann Protocol - a culmination of years of non-clinical research leading to the first-ever, scientific guide to personalized deceleration of the aging process.

Dr. Olivia Lesslar

Medical Doctor, TEDx Speaker & NYC Journal 50 Under 50 (Global)

Dr. Olivia Ly Lesslar is an Australian medical doctor who specializes in complex chronic conditions including neurodegeneration, "mystery illnesses", atopy, cancer, and psychoneuroendoimmunology - the intersection of psychology, hormones, the nervous system, and the immune system. After her medical residency in Australia, she worked across the USA: First with double-board certified neurologist and psychiatrist Dr. Jay Lombard at the Neuroimmunology Associates of New York and currently, with Dr. Chris Renna at LifeSpan Medicine, Los Angeles. Since 2020 she has spent more time in her home country of Australia, and now works with internationally renowned Professors - neurosurgeon Charlie Teo and immunologist allergist Pete Smith at their respective clinics. In 2022, she was featured in the NYC Journal 50 under 50 as a distruptor in her industry.

Amy Lamotte

Clinical Nutritionist (Hong Kong)

Amy Lamotte is the Managing Director of Vallotte Nutrigenomics Limited in Hong Kong, where she splits her time between clinical nutrition and nutrition research. Her clinical practice is focused on personalized nutrition for autoimmune and chronic inflammatory conditions. She devotes half of her time to research in order to contribute to our understanding of how nutrition is the key to creating vibrant health at any age. Her current research interests include nutrition for modulating the immune system and increasing healthspan, nutritional genomics, circadian biology, and the microbiome. She has a Master's of Science in Human Nutrition (summa cum laude) from the University of Bridgeport and a J.D. from Yale Law School.

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