Martin Blaser, 66, and Glenn Webb, 72, often discuss aging on their long summer hikes up to the Continental Divide near Fraser, Colorado. Not their own, but rather that of the human population.
No other species has such a long, extended period of aging past the age of reproduction, or senescence. The two long-time collaborators often wondered and debated while they walked, why would evolution have selected such an age structure for the human population? After all, when resources are limited, the more mouths to feed past the age of reproduction, the greater the burden on the young’s survival.
Blaser, a microbiologist at New York University Langone Medical Center who has spent 30 years studying the commensal gut microbe Helicobacter pylori, decided to view the question from the symbiont’s point of view. Although a peaceful co-existor for much of our lives, H. pylori is a major cause of stomach cancer and that risk increases with age. In some parts of the world, the disease accounts for 7-8% of total mortality.
“That’s a lot for one disease and one microbe,” says Blaser. He thought that perhaps our microbes, involved in most everything we do, might also be involved in our biological clocks. “I began to think that a real symbiont is an organism that keeps you alive when young and kills you when you are old. That’s not particularly good for you, but it’s good for the species .” It’s also beneficial to the microbe community to keep the human population healthy, because if the human population crashes completely, then no more microbial homes.
Webb, a mathematician at Vanderbilt University, could devise a mathematical model to test this hypothesis. Webb’s forte is coming up with nonlinear differential equations to describe dynamic biological processes.
“Differential equations are all about change,” says Webb. “There’s a kind of magic in them that relates different rates of change to each other. And that relationship between them, the combination of those rates acting together, can reveal something unintuitive or unappreciated about the entire biological process.”
Webb and Blaser incorporated three types of mortality into their model of an early human, hunter-gatherer population: all-cause mortality, the mortality created by the burden of a large senescent population on the juvenile population, and finally the mortality associated with particular microbes. Running a baseline version of the model, with the microbial mortality component set to zero, the team showed in a study published this week that the population stabilizes at around 200 years with about 7,000 individuals and a mean age of 18.
Using this baseline model, they next tweaked the starting parameters, such as doubling the fertility rate. Intuition says that boosting fertility should help more juveniles survive and the population thrive. But surprisingly, it causes wild oscillations in the population over time.
“You get into a boom or bust cycle and the oscillation is so great that the population can easily reach extinction,” if a low point coincides with a crisis such as a food shortage , says Blaser. “This might help explain why modern hunter-gatherers don’t have 20 kids, but rather six on average.”
If a higher birth rate was not the answer, perhaps another solution would be to increase the mortality affecting only senescent individuals. Enter the microbes.
Blaser and Webb ran the model, adding in mortality risks based on particular microbial profiles. In one version they added a Shigella-like risk, which increases mortality only for children, and the population crashed to zero.
Next, they ran a version incorporating risk from a microbe like H. pylori, which affects older adults and increases with age. At the same time, they held juvenile mortality to a constant, low level. In this scenario, the human population reaches a stable equilibrium.
“If you have an organism that preferentially kills old people, then you get a robust population,” says Blaser. “This is what Nature is doing,” he argues.
Webb says the modeling also revealed an underlying truth about human population growth—that we have the right fertility and mortality rates to maintain our species, even with our very unusual age structure of prolonged juvenile and senescent phases. “That’s what mathematics does for you. It verifies that our age structure is very stable and has been for a very long time.”
Blaser envisions a phase shift in our relationship with our symbiotic microbes over our lifetimes. Early on, natural selection has favored organisms that aid digestion or other metabolic functions and those that help protect against pathogenic invaders. But as we age, selection favors organisms that begin contributing to inflammation and degenerative processes. He points to species like Bacteroides that make vitamins for us, but if they escape the gut, can kill us.
In modern times of increased longevity, the cancer, inflammation, and degeneration these microbes cause place a major burden on the aging population. “Living with diseases caused by various microbes is inherent in our species,” notes Webb. “But the question is, can we improve longevity or manage it better?”
Blaser cautions that simply getting rid of microbes that cause mischief late in life may not be the best solution—especially if their beneficial effects on immunity and metabolism in early life aren’t fully understood.
“Our relationship with microbes is a fact of life in all directions.”