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• Posted April 6, 2023

Immune System May Hold Secret to Living to 100

Centenarians might live 100 years or more thanks in part to a more agile and adaptive immune system, a new study reveals.

Blood tests of seven centenarians -- average age 106 -- found they possess highly functional immune systems that adapt readily to infections and illnesses, according to researchers.

"What we basically found is that centenarians manifest a history of exposure to natural environmental immunogens that made them more resilient and more resistant to potential harmful factors,"said co-researcher Stefano Monti, an associate professor of medicine and biostatistics with Boston University.

For the study, researchers performed genetic analyses on a broad category of immune cells that circulate in the bloodstream, Monti explained.

They then compared the centenarians' cells with two publicly available databases containing immune cell genetic analyses of another seven centenarians as well as 52 other people ranging in age from 20 to 89. The results were published March 31 in The Lancet medical journal.

Advanced computational techniques allowed the researchers to look for differences between the centenarians and other people.

"It's almost like a detective story, because through analysis of the immune system we can deduct that they've been exposed to multiple infections and multiple sources of harm, and their immune system was capable of mounting an effective response,"Monti said. "And as a consequence, of course, that allows them to live longer, but also they basically built up a more effective immune system to make them more resilient and more likely to live longer."

The researchers found the centenarians' immune profile did not follow the path associated with natural aging.

The researchers also detected cell type signatures specific to exceptional longevity, including increased expression of a gene known to be involved in the body's response to damaged DNA.

The immune system is only one factor that contributes to extreme longevity, but these types of observed differences could be occurring in all of a centenarian's cells, said Dr. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City.

"The same mechanism that makes the immune system better are things that make all their cells better,"Barzilai said.

Monti couldn't say if these differences are driven by genetics, lifestyle, happenstance or some combination of factors. But he said this sort of analysis is needed to figure out how to confer the benefits of longevity to more people.

"This study does not allow us to pinpoint a specific cause of this longevity. It just tells us some of the factors that seem to be associated with extreme longevity,"Monti said. "For example, in order to increase our healthy lifespan, we might need to intervene in boosting a person's immune system."

However, other researchers said that the study, while interesting, didn't provide much enlightenment regarding the causes of these folks' longevity.

"I don't think it tells us anything about why they might have lived so long. I think what it does show us is that there's something special about them,"said Steven Austad, a professor of aging research with the University of Alabama at Birmingham.

Centenarians tend to develop diseases later in life, and are more likely to be completely healthy right up to the day they die, Barzilai said.

"You know, 30% of them don't get any disease when they die,"Barzilai noted. "Some of them just don't wake up."

The problem is that no one is examining these folks at an earlier age because it's not known they will live to 100 and beyond.

"If we had blood from these same people when they were 70 and 80 and 90 and 100, then that would tell us a great deal about the way that the immune system functions in them,"Austad said. "And if we compared them with people that were 70 years old but then died by the age of 80, that would tell us something that's very functional about the people that lived to be 100 years old."

Austad and Barzilai noted that more useful studies are underway that follow the children of centenarians.

"If you're a son or a daughter of somebody who's lived to be 100 years old, your chances of living to be a 100-year-old are increased by 30-fold,"Austad said. "Now you have a 70-year-old that has a fairly high chance of living to 100, and you can compare them to another 70-year-old without that longevity in the family. That is a much more powerful way to get at what's special about these people."

More information

The University of Washington has more about extreme longevity.

SOURCES: Stefano Monti, PhD, associate professor, medicine and biostatistics, Boston University; Nir Barzilai, MD, director, Institute for Aging Research, Albert Einstein College of Medicine, New York City; Steven Austad, PhD, professor, aging research, University of Alabama at Birmingham; The Lancet, March 31, 2023