New findings by researchers at the Stanford University School of Medicine may help explain why older people’s immune systems often decline in function, why different people’s immune systems age at different rates, and indicate that environment matters more than heredity in generating these differences. The study was published today in Cell.
The discovery was made using a modified mass cytometry technique to analyze epigenetic marks on immune cells’ histones, proteins involved in DNA packaging. The researchers hypothesized that epigenetic changes might be the driving factor between immune system differences.
"The immune system plays a prominent role in all kinds of diseases," said Purvesh Khatri, PhD, assistant professor of biomedical informatics and of biomedical data science. "By focusing too heavily on genetics, we're ignoring the implications of human immunology and environmental influences that act on it."
Before making their determinations, the researchers first had to spend more than a year designing molecular barcodes that could be used to specify the amounts of each of 40 different types of epigenetic marks and 30 additional identifying features in 22 different immune cell types, using mass cytometry. After another year of applying the technique, they were left with some 21.7 billion data points. Specialized analysis techniques were developed to interpret this huge amount of data.
It was determined that for many immune-cell types, older people’s cells contained substantially more histone marks than their younger counterparts. Additionally, older people had more cell-to-cell variation in how their histones were marked up.
To further support their findings, blood samples from identical and fraternal twins were analyzed for differences in histone-markings. Histone-marking patters were observed to diverge substantially in older identical twins compared to younger twin pairs. These differences were similar to the differences in genetically unrelated people. Data analysis indicated that this divergence is due to noninheritable factors such as food, sleep, exercise, infection, job, stress levels, and more.
The team plans to continue to examine these patterns; they speculate that histone-mark analysis may someday lead to drugs that reverse these histone-mark deviations in immune cells to treat diseases characterized by these deviations.