The findings, reported this month by researchers from Ohio State University and the federal National Institute of Aging, were published in the Journal of Immunology.
These are the latest results from a nearly three-decade-long program at Ohio State investigating the links between psychological stress and a weakened immune status. Previous studies have examined medical students, newlyweds, divorced spouses, widows, widowers and long-married couples, in each case, looking for physiological effects caused by psychological stress.
In their recent study, Ronald Glaser, a professor of molecular virology, immunology and medical genetics, and Jan Kiecolt-Glaser, a professor of psychology and psychiatry, teamed with Nan-ping Weng and his research group from the National Institute of Aging.
Earlier work by other researchers had shown that mothers caring for chronically ill children developed changes in their chromosomes that effectively amounted to several years of additional aging among those caregivers.
That work, remarkable as it was, looked only at a broad community of immune cells without identifying the specific immune components responsible for the changes. The Ohio State-NIA team wanted to identify the exact cells involved in the changes, as well as the mechanisms that caused them.
They focused on telomeres, areas of genetic material on the ends of a cell's chromosomes. Over time, as a cell divides, those telomeres shorten, losing genetic instructions. An enzyme - telomerase - normally works to repair that damage to the chromosome, Glaser said.
"Telomeres are like caps on the chromosome," said Glaser, head of Ohio State 's Institute for Behavioral Medicine Research. "Think of it as a frayed rope - if the caps weren't there, the rope would unravel. The telomeres insulate and protect the ends of the chromosomes.
"As we get older, the telomeres shorten and the activity of the telomerase enzyme lessens," he said. "It's part of the aging process."
For the study, the researchers turned to a population of Alzheimer's disease caregivers they had worked with before, and compared them with an equal number of non-caregivers matched for age, gender and other aspects. They analyzed blood samples from each group, looking for differences in both the telomeres and the enzyme, as well as populations of immune cells.
"Caregivers showed the same kind of patterns present in the study of mothers of chronically ill kids," Glaser said, adding that the changes the Ohio State/NIA team saw amounted to a shortened lifespan of four to eight years.
"We believe that the changes in these immune cells represent the whole cell population in the body, suggesting that all the body's cells have aged that same amount."
The caregivers also differed dramatically with the control group on psychological surveys intended to measure depression, a clear cause of stress.
"Those symptoms of depression in caregivers were twice as severe as those apparent among the control group," Kiecolt-Glaser said.
"Caregivers also had fewer lymphocytes," Glaser said, "a very important component of the immune system. They also showed a higher level of cytokines, molecules key to the inflammation response, than did the control group."
Other experiments showed that the actual telomeres in blood cells of caregivers were shorter than those of the controls, and that the level of the telomerase repair enzyme among caregivers was also lower.
Kiecolt-Glaser said that there is ample epidemiological data showing that stressed caregivers die sooner than people not in that role.
"Now we have a good biological reason for why this is the case," she said. "We now have a mechanistic progression that shows why, in fact, stress is bad for you, how it gets into the body and how it gets translated into a bad biological outcome."
Much of the Ohio State work is now shifting to studies on how to intervene with that stress in hopes of slowing the weakening of the immune system in highly stressed people.
This research was supported in part by both the National Institute of Aging and the National Institutes of Health. David Beversdorf and Bryon Laskowski, both at Ohio State, and Amanda Damjanovic, Yinhua Yang, Huy Nguyen and Yixiao Zou, all with the National Institute of Aging, worked on this study.