There is a group of genetically “super” people that live among us. They are very rare; only about 1 in every 5 million people would qualify. You could not pick one out in a crowd. You would not know one if you were to pass one on the street. The only telltale sign is that they tend to look much younger than their chronological age. These “super” people have the ability to live extremely long lives. They are called supercentenarians because they are the longest lived of the centenarians, making it to 110 years and beyond. They are quite extraordinary not just because of their long lifespan but also because of their remarkable resistance to disease. They manage to escape the usual degenerative diseases associated with aging such as heart disease, stroke, cancer, diabetes, osteoporosis, arthritis, and Alzheimer’s. We know, from studying the supercentenarians that their long life is largely the result of their genetics because they do not share common environmental or behavioral traits that might account for their longer healthier lives. Indeed the most common trait is an avoidance of doctors. We also know that the offspring of supercentenarians are long-lived (but not their spouses who are exposed to the same environment). Indeed recent evidence points to a slower biological clock ticking in the cells of long-lived people. But no one knows the mechanism that leads to this slower intrinsic rate of aging enjoyed by supercentenarians. If we did, then we might be able to confer long life and healthspan to everyone that desired it.
A lot can be learned from comparing diseased and healthy cells in a dish. Models for human diseases, the so called “disease in a dish” can be engineered using cellular reprogramming techniques to transform normal human cells into pluripotent stem cells. These all powerful pluripotent stem cells can then be converted to any of the many cell types found in our bodies. A model for Alzheimer’s disease for example can be created from the skin cell of a patient that is reprogrammed to pluripotency then converted to neurons to see how Alzheimer’s patients neurons behave compared to normal neurons. The same cells can also be used to screen for drugs to treat Azheimer’s disease. Mandala Biosciences is turning this concept on it’s head to study not disease but extreme resistance to disease. We are modeling the cells of the healthiest people on the planet to determine the molecular mechanism of extreme health and longevity. Ultimately, we aim to identify drugs that will enable all of us to enjoy longer lives with freedom from degenerative diseases associated with aging.