Biomarkers of Aging

Biomarkers of Disease

The use of biomarkers to diagnose and monitor disease is the model for biomarker research. A useful example of biomarkers in medicine comes from endocrinology, where glycated hemoglobin is used as an indicator of long-term blood glucose. A biomarker is useful in this case because long-term blood glucose levels are difficult to measure accurately and oral glucose tolerance tests for diabetes require patients to fast, making the tests somewhat difficult to administer. However, tests of the level of glycated hemoglobin (Hba1c) do not require fasting, are simple to perform, and can be interpreted as the average level of [Page 78]circulating glucose over the previous 60 to 90 days. Although tests of glycated hemoglobin cannot take the place of more complex measures in a complete diagnosis of diabetes, they can provide a useful initial indicator of the interaction between diet and metabolism and thus be a useful biomarker of long-term blood glucose.

A variety of biomarkers have been used to study other age-related diseases, including cancer, Alzheimer's disease, and cardiovascular disease. Biomarkers are used in a variety of ways: to assess exposure to risk factors (e.g., exposure to carcinogens), to gain insight into disease mechanisms (e.g., the role of inflammation in Alzheimer's disease), to understand susceptibility to a disease (e.g., genetic risk), to diagnose diseases (e.g., the use of blood pressure to diagnose hypertension), and to make treatment decisions and assess risk of disease outcomes among those who already have a disease (e.g., monitoring lipid levels in patients with atherosclerosis). The use of biomarkers in clinical practice is rapidly expanding as new and better markers of disease risk are being developed.

Biomarkers of Physiological Processes

Just as biomarkers can be used to study disease processes, biomarkers can shed light on normal physiological changes with age. For instance, the stress response in the hypothalamic–pituitary–adrenal (HPA) axis becomes increasingly dysregulated and inefficient with age. HPA axis activity is complex, involving a range of stress hormones and responses. Cortisol is a stress hormone that is highly responsive to changes in environmental stressors and can be easily collected in saliva or urine, making cortisol a useful biomarker of the stress response. Using cortisol as a biomarker of stress allows one to make comparisons of the stress responses across individuals and to look for factors that moderate this response. However, there are limitations to this approach. Cortisol is simply a marker of a much more complex stress process, and levels of cortisol can be affected by other factors, such as genetics and metabolism, in addition to stress. For this reason, it is sometimes helpful to use multiple markers of a complex process.

A great deal of what is known about age-related changes in the immune system comes from research using multiple biomarkers to understand different dimensions of the immune system. One important biomarker of immune function is T-cell count. T-cells attack infected or damaged cells and mobilize other parts of the immune system. Although the total number of T-cells remains fairly stable with age, the number of functioning T-cells declines and T-cells in older people take longer to renew than they do in younger people. These findings offer potential explanations for reduced immunity among older adults. In addition, increases in inflammatory proteins, such as interleukin 6 (IL-6) and C-reactive protein (CRP), have been observed with age. These proteins are part of the acute phase response to injury or infection but appear to be chronically elevated among older people and may contribute to the development of chronic disease.

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