It’s no small secret that we humans, for the most part, want to live a long life. It’s a preoccupation reflected in movies like the 2015 Age of Adaline and Amazon’s sci-fi series Upload. On the real-life science side, researchers have been cracking away at the longevity code, parsing out how biological factors like sleep, nutrition, exercise, and genetics come together to extend our golden years and make them more livable. Recent research suggests that the quest might not be futile, as scientists believe that we haven't yet reached our maximum lifespan.
But the answer to eternal youth may not have anything to do with us but rather the microbial houseguests living among and within us.
In a study published earlier this month in the journal Nature Aging, researchers in China looked at the gut microbiomes of centenarians — individuals who’ve reached or surpassed a century in age — and compared them against old, middle-aged, and young adults and found these individuals carry microbes associated with youthfulnesses. For example, they found Bacteroides, a common gut bacteria known for its ability to break down complex carbohydrates and fibers. The results also suggest that the gut microbial diversity of centenarians is higher than that of other older adults, which might be why these super-agers are, well, super at aging.
“It’s a wonderful first study to look at that specific age group,” Ruchi Mathur, director of the Diabetes Outpatient Treatment and Education Center at Cedar-Sinai Medical Center, who was not involved in the study, tells Inverse. “I think we need to do more work to see what’s important here to define and build it better and use that work to enhance human health and longevity.”
Better bugs, longer life
You might be aware of the microbiome due to emerging scientific research and the popularity of supplements like probiotics, but here’s a recap: The microbiome is a vast and diverse collection of microorganisms — both bacteria, viruses, fungi, and other microbes — found on every surface and crevice in and on your body such as your skin, nose, and gut that are in regular contact with the outside environment.
These microorganisms, seeded at birth (a gift from your mom) and molded as we age, are important for many bodily functions, including digestion and immune system regulation, and central to mental health, fighting cancer, sleep, and much more.
Scientists have found that as we age, so too does the makeup of our gut bugs. As time passes, the diversity — the individual species that make up the microbial neighborhood — changes, with a decline in some beneficial bacterial species and an uptick in others that are associated with inflammation and disease, says Mathur and Hariom Yadav, director of the University of South Florida’s Center for Microbiome Research. This shift in the gut balance may contribute to age-related diseases such as Alzheimer's, cardiovascular disease, and cancer. For example, some studies have found that changes in the gut microbiome can lead to chronic inflammation, which is a risk factor for many age-related diseases.
Humans aren’t alone in this microbial shifting as we age phenomenon — it’s also been observed in other animals like flies, fish, and mice. In studies transplanting specific bacteria or poop from a young animal into an older one — researchers have done this using fish and mice, for example — the gut swapping appeared to improve the animals’ overall health and lifespan. These sorts of studies suggest that interventions targeting the microbiome could be a promising approach to combating age-related decline and diseases.
Unfortunately, youthful poop transplants as an anti-aging antidote aren’t as straightforward in humans. Not only are human clinical studies often limited by ethical and practical considerations, but the microbiome’s overall composition can also be affected by numerous factors, such as diet, lifestyle, genetics, and environmental factors, all of which make it challenging to isolate and identify the specific effects of the microbiome on longevity.
But this is where centenarians come in — since they’re still kicking, there has to be some secret hiding in their microbiomes. Studying the 100+ Club (those over 100 years old) has helped scientists identify specific bacterial species within the microbiome and metabolic pathways that may be associated with healthy aging and longevity. For example, in a 2017 study published in the journal Mechanisms of Ageing and Development, the microbiomes of centenarians in Japan and Italy were found to share similar microbial features, despite differences in diet and lifestyle, such as a higher abundance of certain bacteria with anti-inflammatory properties.
Aging like fine wine
So while the idea super-agers have a super-charged microbiome isn’t a new discovery, ongoing research is crucial to better resolving the keys to unlocking longevity, especially as we don’t exactly have a surplus of century-old senior citizens to go around.
In the new study out of China, the researchers took poop samples from over 1,500 individuals across a wide age spectrum — the youngest at 20 years old and the eldest at a whopping 117. The participants were divided into five age groups — age 22 to 44 years, age 45 to 65 years, age 66 to 85 years, age 90 to 99 years, and age 100 to 117 years — and the gut bacteria found in their stool was compared. There were also four control groups of individuals ages between 20 and 85 and 90 and 99 years of age.
Aside from comparing different age groups, the researchers selected 45 centenarians to follow over a year and a half to see how their microbiomes in terms of microbial structure, composition, and diversity. (Poop samples were taken right at the start and a year and a half later.)
The study ultimately revealed four different groups of gut microbiomes, called enterotypes, based on the levels of different types of bacteria. It seemed regardless of health status, the centenarians had a unique enterotype that is a combination of the two found in young adults aged 20 to 44 — Bacteroides — and older adults — Escherichia and/or Shigella. This youthful enterotype, in particular, was structured similarly to young adults in that centenarians had a higher evenness of species, a measure of how close in numbers each species in a community are (with a higher number indicating different bacteria are about equally abundant).
In the longitudinal study, centenarian microbiomes kept on changing as they age, but in a good way, backing up the comparison study. The researchers saw there seemed to be a trend toward preserving certain beneficial Bacteroides species that foster a healthy and stable gut microbiome, and less so the bugs that have the potential for becoming pathogenic under certain circumstances.
Predicting longevity from a microbial snapshot
The researchers of the new study say that this unique microbiome “fingerprint” could potentially be used to predict who’s likely to live past 100, but it’s important to bear in mind that the results aren’t clear as to how exactly this microbial pattern is linked to longevity since there’s no delineation of cause and effect, says Mathur.
“What would have been nice was a blood sample,” she says. “If we had blood samples, we could have seen [the centenarians’] markers of inflammation or their LDL [low-density lipoprotein] and cardiovascular profile, something that would link the changes that you’re seeing in the microbiome with something that’s physiological.”
There’s also the issue of how much genetics is influencing the microbiome of these long-lived individuals since there’s a dynamic interplay between our bodies and our bacterial tenants. Mathur posits centenarians could be genetically predisposed to live longer, and that influence may be exerted on the microbiome. Additionally, Mathur says there’s an external effect of diet and nutrition, which isn’t made clear in the study. Theoretically, centenarians could just be eating a healthier diet that favors a well-rounded gut microbiome. But more so, there’s the issue of how generalizable these findings are for human longevity across a planet filled with people with no two similar microbiomes.
“This is a really important point here because people living in different geographies have a different standard for the microbiome,” Yadav of USF tells Inverse. “The microbiome which might look healthy in a U.S. population might not be healthy for a Japanese population and vice versa.”
Yadav says one part of the equation of connecting the microbiome to longevity is discerning what a standard, healthy microbiome looks like across the board. Once we do that and see which bacterial species remain the same for centenarians, regardless of where they are in the world, that might be the fountain of youth jackpot. Bacteroides might be one of them, as the study suggests, but there are likely many other gut microbes out there that play a beneficial role as well.
With personalized medicine on the rise, Mathur and Yadav say these and other studies could help usher in special bacterial cocktails meant for specific age groups to maintain your health (like living longer) or to address a certain medical need, such as lowering blood pressure or cholesterol. Again, that still requires more research to pinpoint what exactly each microbial species is doing in our bodies and how.
Until then, it might be best to eat your way to a healthier, happier gut microbiome. Who knows, maybe you might actually live longer.
