Most of us strive for a long—and healthy life. However, some individuals maintain excellent health in their 80s and beyond while others develop significant health problems decades earlier. A new study by researchers at the Department of Integrative Biology and Physiology, University of California, Los Angeles found some clues for this disparity in the makeup of intestinal bacteria. Their study suggests that analyzing intestinal bacteria could be a valuable method to predict health outcomes as we age. They published their findings online in the journal Cell Reports.
The investigators used fruit flies, which typically live for about eight weeks; however, some live to an equivalent age of 80 to 90 human years. In addition, their genetic makeup has been used for research for decades. All of the fruit fly’s genes have been identified and researchers know how to switch individual ones on and off. In the study, the investigators discovered changes within intestinal microbes that precede and predict the death of the fruit flies.
“Age-onset decline is very tightly linked to changes within the community of gut microbes,” explained senior author David Walker, a UCLA professor of integrative biology and physiology. He added, “With age, the number of bacterial cells increase substantially and the composition of bacterial groups changes.” In a previous study, he and his colleagues discovered that five or six days before flies died, their intestinal tracts became more permeable and started leaking. The new study entailed analysis of more than 10,000 female flies; the investigators found that they were able to detect bacterial changes in the intestine before the leaking began. Some of the fruit flies were given antibiotics that significantly reduce bacterial levels in the intestine, and the researchers found that these medications prevented the age-related increase in bacteria levels and improved intestinal function during aging. They also found that reducing bacterial levels in old flies can significantly prolong their life span.
“When we prevented the changes in the intestinal microbiota that were linked to the flies’ imminent death by feeding them antibiotics, we dramatically extended their lives and improved their health,” explained Dr. Walker said. (Microbiota are the bacteria and other microorganisms that are present in humans, other mammals, fruit flies and many other animals.) The fruit flies with leaky intestines that were given antibiotics lived an average of 20 days after the leaking began, which represented a significant portion of the insect’s life span. On average, flies with leaky intestines that did not receive antibiotics died within a week. “The health of the intestine, in particular the maintenance of the barrier protecting the rest of the body from the contents of the gut, is very important and might break down with aging,” explained lead author Rebecca Clark, PhD.
Drs. Walker and Clark collaborated with William Ja, an assistant professor at Florida’s Scripps Research Institute, and Ryuichi Yamada, a postdoctoral research associate in Ja’s laboratory, to produce a group of flies that were completely germ-free, with no intestinal microbes. Those flies were found to have a very dramatic delay in intestinal damage, and they lived for about 80 days, approximately one-and-a-half times as long as the insect’s typical life span. Researchers have recently begun to link a wide variety of diseases, including diabetes and Parkinson’s disease, to changes in the microbiota, but they do not yet know exactly what healthy microbiota look like. “One of the big questions in the biology of aging relates to the large variation in how we age and how long we live,” noted Dr. Walker; he also stated that scientific interest in intestinal microbes has exploded in the last five years. He explained that when a fruit fly’s intestine begins to leak, its immune response increases substantially and chronically throughout its body. Chronic immune activation is linked with age-related diseases in people as well.
Dr. Walker noted that the study could lead to realistic ways for scientists to intervene in the aging process and delay the onset of Parkinson’s disease, Alzheimer’s disease, cancer, stroke, cardiovascular disease, diabetes and other diseases of aging. He cautioned that significant progress in this research could take many years.
