If those ubiquitous TV infomercials are to be believed, a person’s age can be determined solely by outward signs, like wrinkled skin, gray hair, and yellow teeth. But according to a team of researchers at the Technion-Israel Institute of Technology and Stanford University, the state of a person’s immune system provides a far more accurate measurement of a person’s health than physical signs or even chronological age. The team has also developed a way to gauge “immune age,” which could bring about new frontiers in personalized medical treatment, drug and vaccine clinical development, and health management and insurance processes.

Over an individual’s life, the immune system declines in function, a process accompanied by an increase in inflammation. This ultimately leads to an inability to cope with infections and a higher risk of chronic diseases such as cancer and heart disease, the leading causes of death among older people. Due to the high complexity of the immune system, no real metric of immunological health exists in the clinic beyond the Complete Blood Count. This lab test, which has been in existence since 1957, enumerates the abundance of immune cells, but at a resolution too low to identify anything but extreme conditions.

Enter the new monitoring system developed by the Technion-Stanford team. Their study characterized annually, at high resolution and with thousands of different parameters, the immune systems of 135 healthy people at different ages over a period of nine years. The researchers collected rich longitudinal data that allowed for the capture a pattern of immune cellular changes occurring over time that are common to all adults, irrespective of individual differences between peoples’ immune systems.

“Individuals varied only at the rate their immune system changes, not in the actual pattern of change,” said Shai Shen-Orr, Associate Professor in the Technion’s Rappaport Faculty of Medicine and lead co-senior author of the study. “This allowed us to map a path of how the immune system ages and to quantify an individual’s immune age. Unlike your actual chronological age, the immune-age is intimately tied to the state of one’s immune system, the body’s chief sentinel. We can therefore capture medically relevant information using immune age that physicians would otherwise miss.”

Using the new method, the researchers quantified the immune age of more than 2,000 adults who participated in the Framingham Heart Study, which has been carried out among people living in the Boston area for more than half a century. By analyzing the data collected on this large sample, the researchers showed that advanced immune age predicts mortality at an older age beyond known risk factors. In other words, although they may be in the same age group, people with an “older” immune system are at higher risk of dying than people with a “young” immune system.

“This paper represents a very important step towards developing useful measures of immunological health, especially as it could help to identify who is at risk for cardiovascular and other diseases,” said Professor Mark M. Davis, Head of the Stanford Institute for Immunity, Transplantation and Infection and the other co-senior author of the study. “It’s been sixty years since the last immunological benchmarks (CBCs) were introduced into general medical practice and so it’s high time we had something much more sophisticated such as we describe here, that reflects the tremendous explosion of knowledge that we have had in the field in this time.”

Because immune age is also affected by genetics, the researchers want to characterize the immune age of populations with a genetic predisposition to a long life, such as descendants of people who passed the age of 100. “By doing so, we may characterize genes that affect immune age,” said Prof. Shen-Orr. “In addition, the method we developed will make possible identification of lifestyle, habits and medications that affect immune age positively or negatively.”

The research was published in the prestigious journal Nature Medicine and was led by Prof. Shai Shen-Orr of the Technion-Israel Institute of Technology and Prof. Mark Davis of Stanford University, with co-first authors, doctoral student Ayelet Alpert and Dr. Yishai Pickman of the Rappaport Faculty of Medicine, together with other Technion and Stanford researchers. The research has been supported by grants from the US National Institutes of Health (NIH-NIAID), the Ellison Foundation, the Howard Hughes Institute, the Israel Science Foundation, the Rappaport Institute and the Kollek and Taub Family Awards.

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