Environment affects immune system as you age
As we get older, our immune systems just don’t work like they used to. Much like people, individual immune cells show signs of their age, looking much different in a 25-year-old than in a 65-year-old. Your genes are to blame for some of this change, but new research suggests your environment might be a bigger culprit.
“Genetically, you and I are more than 99 percent identical,” said Alex Kuo, a senior author of the new study from Stanford University. “What you eat, how much stress you have, how well you sleep — all these environmental influences explain the differences” in how our immune systems age.
The research published in “Cell” on Wednesday compared the immune cells of young people and older adults, looking specifically at their DNA — the instruction manual carried by every cell in the body. In young people, immune cells follow this manual to the letter and get the job done. But in older people, these instructions get fuzzy. Though the contents of our DNA don’t change much over time, the study suggests our cells read its directions differently.
About 70 percent of this change is caused by environmental factors, such as your occupation, where you live and whether you smoke, said Kuo. Even twins with identical DNA show unique differences in their immune cells over time. This is important because unlike genetic mutations, these environmental effects “are mostly reversible,” he said. If doctors could reverse these changes in the aging immune system, they could bolster older patients against a multitude of diseases.
“Older people tend to have chronic inflammation, they respond less well to infection,” said Francesco Vallania, a lead author of the study. Older people also have a higher incidence of cancer and autoim-
“If the cells are changing, then it could be a way to detect potential markers of aging.” — Bérénice Benayoun, assistant professor of gerontology
mune disorders because of their weakened immune systems, he said. “This is something we observe in immunology on a daily basis.” The researchers are planning follow-up studies to determine exactly which environmental factors heighten peoples’ risk for these conditions.
Not everyone develops these common immune deficiencies as they grow older — some people age better than others. Even between twins, one may stay perfectly
healthy in their 70’s while the other develops cancer. If their DNA is the same, how does this happen?
“Cells from the head have the exact same genomic DNA sequence as cells from the toes,” said Kuo. Though all cells have the same DNA, they use information from different chapters to build proteins and perform tasks. Structures called histones, which DNA wraps around, help determine what chapter cells flip to and when. Histones are highly influenced by environmental factors, like fluctuating hormones or exposure to
infection, and they are constantly modified as we age. As these changes accumulate in our immune cells, he said, they might leave the body less equipped to ward off disease.
The researchers looked at billions of immune cells to reach this conclusion, doing so with the help of new technology.
“I think this is a landmark study,” said Bérénice Benayoun, an assistant professor of gerontology at the University of Southern California. Most prior research has looked at cellular marks of aging in bulk, rather than at the level of individual cells, she said. But there
are many types of immune cells, and there’s a theory that each of their proteinbuilding signals become “noisy” with age. The Stanford study was the “first” to look at how the environment might alter these signals in single cells, she said.
“If the cells are changing, then it could be a way to detect potential markers of aging and give us insights into why those cells are becoming dysfunctional,” she said.
Each blood sample the researchers took provided them millions of cells to study. “Someone gives us a blood sample, we take the immune cells and for every
single one of them we measure chemical modifications” to their histones, said Vallania. “The number of data points is equal to the size of the human genome — actually, bigger,” he said.
From all that data, the researchers picked out distinct patterns of change. These tell-tale “fingerprints” showed up much more in older people than younger, said Vallania. The changes cropped differently between different people, and even between individual immune cells. These characteristic markings are mostly a product of age and a person’s environment, said Kuo, and could
lead to diseases like cancer, depending on which marks are made.
Some medications already exist to help clear up these chemical marks, specifically with the goal of reducing patients’ risk of cancer. Stanford researchers are currently investigating whether other agerelated diseases have their own unique signatures, and whether drugs can be developed to erase them.
“Potentially understanding what those changes are means that we might be able to correct them,” said Benayoun, “and in the long term, restore healthy young tissues.”