Shin-ichiro Imai

Shin-ichiro Imai, MD, PhD

Personal information Born 1962 (age 58) Tokyo, Japan Nationality Japanese Education Keio University School of Medicine (PhD, MD) Field of study Molecular mechanism of aging and longevity Occupation Researcher, professor Affiliation Washington University School of Medicine in St. Louis Position Professor of Developmental Biology and Medicine

Shin-ichiro Imai is a researcher and physician at the Washington University School of Medicine where he is a professor of developmental biology specializing in anti-aging. After an early childhood interest in the sciences, Imai went on to pursue a medical degree at Keio University in Tokyo. Over half way through, however, Imai became torn over his increasing desire to be a researcher into cellular senescence, which is the study of how cells age and break down.

After joining with Massachusetts Institute of Technology researcher Leonard Guarentes lab, he and fellow researchers went on to make significant progress in the study of anti-aging, starting in the 1999 discovery of the role of sirtuins in the metabolic regulation of cells. His work has continued to focus on the physiological processes that cause living cells to stay young and healthy, and focus on discovering supplementation that could reinforce the delivery and creation of anti-aging compounds within the human body.

Early life and research

Shin-ichiro Imai was often told the story of his birth by his parents: because of his mothers partially detached placenta, his chance of surviving birth was lower than normal, and his parents had to find a doctor willing to take on the risk. This story influenced him in later life to want to become a doctor. A self-described “active child”, he was given many biology projects by his history-teaching father, including one that involved tracking the height and petal sizes of sunflowers, which they grew and recorded. Imai attended Keio University in Tokyo with the intention of becoming a medical doctor, but in year four of six of his studies, he began to take an interest in research. After much questioning of which path to take, Imai finished his medical degree and began his doctoral work while working full time at the laboratory he had been volunteering at for years.

Imai was fascinated by the relatively un-researched area of cellular immortality, which asked how cells have, and then lose, the ability to endlessly self-replicate, and how this ability might relate to both human lifespans and health risks like cancer. After a difficult start over the next two years setting up complex experiments to track the activation of different genes, he successfully discovered a protein called collagenase, later found to be part of a group of proteins that are involved in cellular senescence. Through his work, he met Leonard Guarente from the Massachusetts Institute of Technology at a scientific conference, and thereafter joined Guarente’s lab at MIT as a post-doctoral student. Imai met and worked with David Andrew Sinclair, a fellow anti-aging researcher and writer, at Leonard Guarentes lab. In 1999, Imai, Guarente, Sinclair, and others discovered how certain metabolic regulation proteins in cells, called sirtuins, silence certain genes when cells are young, and cease this ability when they grow old. This function was found to be dependent on the levels of energy in cells, and greatly influences cellular longevity.

Research

In 2001, Imai joined the faculty of Washington University in Saint Louis. Imai’s research into the nature of aging continued there, and in 2011 he published a study showing that giving female type 2 diabetic mice a compound called nicotinamide mono nucleotide (NMN) helped restore them to a healthy metabolism. The chemical compound also helped with other age-related conditions. Imai believes that the chemical NMN, which is derived from Vitamin B3, is used in the production of “NAM”, the loss of which is theorized to cause aging. Foods thought to be high in NMN include broccoli, edamame, cucumber, cabbage, and avocado, though Imai doesn’t believe that any of the foods would affect your rate of aging significantly.

Imai did further research in 2013 on sirtuins, and found that supplementing the compound NMN did not stop the aging process, but helped extend the period of youth in mice. He also discovered that a sirtuin protein found in the brain, named “Sirti1”, was responsible for, and seemed to replicate, the effects of low-calorie diets. Many age-related health issues, such as declines in physical activity, body temperature, and other issues were also delayed by supplementation with this protein.

Imai also explored the question of optimal levels of fat the human body should have, and found that as humans grew older, being slightly overweight was more desirable than being at “healthy” fat levels. Imai has hypothesized that fat cells somehow effect the regulation of the body’s physiology, possibly through the hypothalamus. In one study, mice that had low levels of “NAMPT” in their fatty tissues also had low levels of “fuel” in their hypothalamus, followed by worse measurements in their physical activity. Imai latter commented on a study involving stem cell injections into the hypothalamus of mice that caused a reduction in their memory loss, stating that the hypothalamus may control the aging and longevity of mammals.

In 2016, Imai partnered with researchers in Japan to study the bio-availability and safety of NMN supplementation in humans. The idea behind this study was to try and “re-energize” the bodies cells and stimulate the restocking of the NAM supply, thereby disrupting the aging process. Imai has explained that, in ways science does not yet entirely understand, sirtuins, along with chemicals like metformin and rapamycin, are all involved in creating cellular energy, but when the process of creating and delivering NAM breaks down, aging is the result.

In 2019, Imai worked on a study involving the injection of young mouse blood into older mice which caused increased longevity. Imai and his team hypothesized that the increased presence of a protein enzyme called “eNAMPT” in younger blood, which helps cells make energy, may have been the cause. Previous studies had focused on giving whole blood to older mice, whereas this study focused just on the enzyme. This chemical had the effect of mimicking calorie restriction without actually having to consume fewer calories. The mice in the study given eNAMPT supplements lived on average sixteen percent longer.

Imai has also studied how the bodies cells react to the loss of the “fuel” that is “NAM”, and how the body attempts to summon more of it when their supply starts to run out. Imai’s research was able to show compound Slc12a8 is the NMN transporter, which had not previously been identified. Imai has noted that the human body ends up in a kind of “bottleneck” as it ages, as the body can no longer produce enough NAD, and yet it needs more than before, which Imai speculates is due to chronic inflammation. He is working with Washington University’s Office of Technology Management and a Japanese company called Teijin Limited to use this knowledge to create therapies both increasing NAD production and helping in the transportation of it throughout the body. Because increased production of NAD can sometimes be used by virulent cancerous tumors, studies in mice continuously look for any rise in the rate of cancer. Imai has also cautioned that longevity and health are sometimes at odds, and continued low calorie anti-aging can lead to fragility, meaning higher susceptibility to disease, as was demonstrated in studies done on nematodes in 2019. eNAMPT levels will also be examined during the study to see if they can serve as a biomarker for age. Research is ongoing in older humans to see if the levels of eNAMPT are different in people who have experienced illness, and if the compound could be used for anti-aging supplementation.