Researchers examined a class of chemical compounds called indoles and found that they have potential for extending vitality in our fellow mammals, mice. The findings could pave the way for a drug that could one day help humans to “live better for longer.”
“Indoles” is the parent name given to a range of chemicals found in nature. The compound occurs in some flowers, such as jasmine and orange blossom, but it can also be found in fecal matter.
Indoles are also produced in our gut by many kinds of bacteria that break down tryptophan, which is an essential amino acid.
New research – led by Daniel Kalman, Ph.D., a professor of pathology and laboratory medicine at Emory University School of Medicine in Atlanta, GA – examines the effect of indoles on improving the “healthspan” of various organisms, ranging from fruit flies to mice.
The term healthspan is used by the authors to mean the “proportion of time that an animal remains healthy and free of age-related infirmities.”
“We need a better understanding of healthspan,” says Prof. Kalman. “With medical advances, people are living longer; but you might not really want to live longer if it means spending those extra years frail and infirm.”
Given our rapidly aging world population, the researcher adds, the health and economic burden that age-related diseases will put on the healthcare system is predicted to skyrocket in the next few decades.
The findings were published in the journal Proceedings of the National Academy of Sciences.
Prof. Kalman and team’s new study builds on their previous research that found that indoles, whose production was mediated by the Escherichia coli bacteria, made mice more resistant to infections and other forms of physiological stress.
For the new research, Prof. Kalman and team fed E. coli to a type of worm called Caenorhabditis elegans. Some of the worms could produce indoles as normal, while another group was genetically engineered not to be able to do so.
The researchers also carried out experiments in mice, destroying their gut flora by administering them antibiotics. They then repopulated the gut microbiome of one group of mice with E. coli, and with bacteria that could not produce indole in the other group.
The findings revealed not so much an increase in lifespan, but an extension of healthspan.
With time, the older worms that had produced indoles were still mobile and active after the age of 15 days. Additionally, these worms had significantly more swallowing strength and were more resistant to heat stress compared with those that did not produce indoles.
Normally, due to aging, after the age of 15 days, all of these abilities are impaired in worms. Also, worms usually stop reproducing after the age of 5 days. The indole-producing worms stayed fertile for almost 12 days, however, suggesting that indoles more than doubled their fertility.
Likewise, in mice, indoles seemed to enable old rodents – or mice that were 28 months old – to maintain youthful and healthy levels of weight, mobility, and activity.
Indoles seemed to extend life in younger mice as well. In a mouse model wherein the rodents were exposed to life-threatening levels of radiation, indole-producing mice lived longer.
The authors write that while there have been other studies to have uncovered genetic pathways involved in increasing the lifespan of various organisms, few of these indicated a way to extend the lifespan while concomitantly extending the healthspan.
“Rather, mutations that extend lifespan often reduce healthspan and increase frailty,” they write.
But the analysis of the genetic patterns activated by indoles in mice and worms showcased in the new study revealed “a gene expression profile in aged animals reminiscent of that seen in the young, but which is distinct from that associated with normal aging.”
“It’s like the Picture of Dorian Gray, in terms of the genes involved […] Indoles make old animals look more like the young ones […] This is a direct avenue to a drug that could make people live better for longer.”
Daniel Kalman, Ph.D.
“Indole is such an ancient messenger,” he adds. “It’s how plants steer their growth, how bacteria talk to each other, and it is how plants and bacteria talk with us and ensure proper homeostasis with our immune system. It is perhaps not so surprising that these molecules help maintain our vitality.”