As you age, the likelihood of chronic inflammation increases, which increases your risk for diseases such as cancer, dementia, and cardiovascular problems. With the help of deep learning, researchers have now identified immune markers in the blood that provide information about the inflammation load and help determine biological age. This “iAge” immune clock can contribute to the early detection of age-related diseases and also offers a starting point for therapeutic interventions.
The immune system plays an important role in our health. It protects us from pathogens and foreign substances and also removes dead or defective own body cells. It often reacts to infections with inflammation, which helps to fight the relevant pathogen quickly. In old age, however, inflammatory processes increase, which arise without external influences and are chronic. This inflammation leads to tissue damage in the long term and increases the risk of cancer, dementia and cardiovascular disease.
Biomarkers for aging
A team led by Nazish Sayed from Stanford University in California has now made use of this knowledge to develop a new biological “age clock”. To do this, they first determined 50 different immune markers in blood samples from 1001 people between the ages of eight and 96. Then they trained an artificial intelligence with the help of deep learning to recognize patterns in the blood results and to relate them to the health data of the test subjects. In this way, they identified biomarkers that are associated with age-related diseases and frailty and thus represent a new biological clock of age: iAge.
“IAge predicts important aging phenotypes and provides insights into the mechanisms that lead to the aging of the blood vessels,” the researchers write. “We observed a significant correlation between iAge and multimorbidity in those over 60 in this study. This underscores iAge’s key role in the accumulation of physiological damage as we age. “
Signal substance causes cells and blood vessels to age
The chemokine CXCL9 apparently plays a particularly important role in aging. This signaling substance of the immune system is normally responsible for attracting lymphocytes to the site of an infection. “In this case, however, we have shown that CXCL9 upregulates several genes that contribute to inflammation and that it is involved in cellular and vascular aging as well as unfavorable changes in the cardiovascular system,” says Sayed.
Sayed and his colleagues also tested what happens when they experimentally switched off CXCL9 on human cells and mice. The result: the vascular function improved, arterial stiffening decreased and the cells were able to renew themselves again. “In the future, it may be possible to delay the onset of vascular aging by therapeutically suppressing CXCL9,” the researchers write.
Can health be predicted?
To further validate their results, they also determined iAge in people who were not involved in the original study, including 19 over centenarians. It showed: “iAge is associated with extraordinary longevity.” While the iAge in people from the control group roughly corresponded to their actual age, the corresponding immune markers in particularly long-lived people were significantly lower than would have been expected. Sayed’s colleague David Furman explains, “On average, centenarians have an immune age 40 years younger than what is considered ‘normal’, and we had one outlier: a super healthy 105 year old man from Italy who had the immune system of a 25 year old -Year-olds. “
According to the researchers, iAge can be used to predict future health status: “With iAge, it is possible to predict seven years in advance who will become frail,” says Furman. “That leaves us a lot of leeway for interventions.” However, the extent to which the method can actually be used in practice remains to be seen. Christian Kosan, head of the transcription regulation working group at the Institute for Biochemistry and Biophysics at the Friedrich Schiller University Jena, who was not involved in the study, points out: “These experiments took place under very standardized test conditions that cannot be guaranteed everywhere. It is also questionable whether the results determined by statistical methods can also be measured and precisely determined in an individual with the same accuracy. This would first have to be checked through field studies. “
Source: Nazish Sayed (Stanford University, California) et al., Nature Aging, doi: 10.1038 / s43587-021-00082-y