The candles on a birthday cake tell people's chronological age, but they don't necessarily reflect a person's health and biological age. Some people seem to age better than others, able to remain active and engaged, doing what they love to do, despite advancing years.

Why does biological age seem to move more slowly for some than others? An international team led by researchers at Washington University in St. Louis looked for answers.

Everyone knows we age differently, researcher Maxim Artyomov, told TheDoctor. We experience aging as what is happening with our hair, skin and physical stamina as we get older. Our immune system can keep us healthy well into old age or increase our risk of age-related diseases. It is a factor in why we age differently, but we haven't been able to see what is happening to the cells of the immune system as the years go by.

An affordable diagnostic tool could make monitoring immune health a regular part of preventive care.

“So this study is like looking in the mirror at our immune system,” Artyomov, the Alumni-Endowed Professor of Pathology and Immunology at Washington University, explained.

To see how people's immune systems change over time, the researchers analyzed about 12.4 million immune cells from more than 2,600 healthy adults between the ages of 20 and 90 years old or older from eight study populations in North America, the United Kingdom, Asia and Australia.

Younger people had more naïve immune cells that had not been exposed to disease-causing bacteria or viruses compared to older people. Older people, however, had more diverse immune systems. Some of them had immune cells that indicated the presence of inflammation.

How well people age was strongly associated with a particular set of immune cells, CD8 effector memory T cells, and more specifically the ratio of granzyme B-producing CD8 cells to granzyme K-producing cells. Granzymes are enzymes that break down proteins. Granzyme B-producing cells destroy infected or cancerous cells. Less is known about what granzyme K-producing cells do, but researchers think they cause local inflammation and launch an immune response by signaling other immune cells.

Younger people had more naïve immune cells that had not been exposed to disease-causing bacteria or viruses compared to older people. Older people, however, had more diverse immune systems.

The researchers developed a computer model to measure the ratio of granzyme B-producing CD8 cells to K-producing cells, then applied this model to 50,000 people from the U.K. Biobank database. The projection showed that people with a higher ratio of granzyme B-producing cells to K-producing cells had a greater risk of mortality in 10 years than those with a higher ratio of K-producing cells to B-producing cells. They were also more likely to have chronic conditions such as high blood pressure, type 2 diabetes, liver disease and kidney failure.

“A ratio that shifts toward more B-producing cells is a sign of unhealthy aging,” according to the researchers. Coauthor Marina Terekhova, an instructor of pathology and immunology at Washington University, explained: “A higher ratio of B-producing cells means the immune system is already reacting to something.” While not a formal diagnosis, it suggests something in the body is off track.

Currently, measuring the ratio of granzyme B-producing cells to K-producing cells in patients on a large scale would require the widespread use of complex and expensive technology. Artyomov and his team hope to develop a blood test that could be processed using equipment now readily available. “An early diagnostic tool to alert physicians to subclinical immune stress could prompt further testing and intervention before chronic disease symptoms appear,” he explained.

The study is published in Immunity.