Could Rapamycin be the best drug to promote gut health and longevity?

What if we could alter our DNA in minutes by simply getting a jab or taking a pill? It might sound like something right out of a science-fiction novel, but recent discoveries have shown that scientists have made some serious headway in the field of genome editing. And these discoveries could potentially revolutionize the field of anti-aging in the near future. A recent study conducted by a joint team of researchers from the Max Planck Institute for Biology of Aging, the CECAD Cluster of Excellence in Aging Research at the University of Cologne, the University College London, and the University of Michigan has successfully managed to demonstrate how rapamycin—a well-known anti-aging candidate—is able to target gut cells and alter the way that DNA storage takes place in these cells. The study, which was carried out on fruit flies and laboratory mice, aims to show how altering DNA in these cells promotes gut health and longevity. It also opens a new avenue of possibilities for specialized therapeutic interventions against aging. DNA is the genetic material that constitutes our ‘essence,’ if we may call it that. It is present in every cell nucleus in our body. In human beings, the DNA molecule is astoundingly two meters long; yet it miraculously fits into the cell nucleus which is only a few micrometers in diameter. How is this possible? Well, it all lies with how DNA is intricately stored. Our DNA is wounded multiple times around a specific set of proteins known as histones. How tightly our DNA is wound actually determines the kind of genes that can be read from our genome. In several species, including ourselves, the concentration of histones in our nucleus declines with age. Until now, scientists were unable to determine whether changes in cellular histone levels were capable of slowing down the aging process in living organisms. However, the drug rapamycin is showing a lot of promise as an anti-aging substance that is capable of extending positive effects on your health, even in old age. In fact, here’s what first author of the study, Yu-Xuan Lu (postdoc in the department of Linda Partridge) had to say about the breakthrough: “Rapamycin turns down the TOR signaling that regulates a wide spectrum of basic cellular activities such as energy, nutritional, and stress status. In short, we use rapamycin to fine-tune the master regulator of cellular metabolism. Meanwhile, we know that histone levels have a critical impact on the aging process. However, we had no idea whether there is a link between the TOR signaling pathway and histone levels, and more importantly, whether histone levels could be a druggable anti-aging target.” To determine the effects that rapamycin had on histone proteins, the team of researchers studied the different organs of the classic Drosophila melanogaster—or commonly known as the fruit fly. They specifically analyzed the organs and tissues of the fly that exhibited notable changes in histone level prior to treatment and after treatment with rapamycin. Which simply meant switching off the TOR signaling pathway. The results were astounding. The fruit flies recorded an increase in histone proteins once rapamycin treatment was subjected. This effect was observed exclusively in the gut of the flies, but not in other organs and tissues. Upon further experiment with laboratory mice, rapamycin was shown to increase the levels of histone proteins in a particular gut cell-type known as enterocytes; which then extended the lifespan of these animals, improved gut health, and reduced tumor growth. Lead author Yu-Xuan Lu notes that these results demonstrate, for the first time, a strong link between histone levels and the TOR signaling pathway. They concluded that an increase in histone protein levels changes how DNA is stored in the nucleus. This not only broadens our understanding of the aging process, but also enables us to provide new opportunities for targeted therapeutic interventions that could reshape how we approach aging altogether.