New Biomarker of Aging Found In β2-Microglobulin From Cheek Cells
β2-microglobulin (B2M) is a type of tumor marker that has now been correlated with cellular senescence and inflammation, which contribute to aging.
B2M rises with age in cells of the inner cheek, correlating with p16 expression (a marker of senescence).
In this study, there was a direct correlation between B2M expression and age, as well as with p16, B2M, inflammatory cytokines, and age.
Researchers here note that expression of β2-microglobulin rises with age in cells of the inner cheek, correlating with p16 expression, a marker of cellular senescence. β2-microglobulin is connected to inflammation, and senescent cell burden is one of the more important contributions to the chronic inflammation of old age. One can never have too many biomarkers of age, even if they are individually only loosely correlated with age, as combining them can in principle produce better and more accurately correlated metrics.
β2-microglobulin (β2M) is a small protein that is expressed in all nucleated cells, previous data showed that its activity increases during inflammation. β2M interplays with cytokines for instance, IL-6, IL-8 and others intracellularly to induce inflammatory responses. In addition, it can bind and modulate the activity of growth factors and hormones and receptors. β2M has been exploited as a biomarker for many disorders with inflammatory components.
Our group previously showed that β2M expressed highly in senescent cells, and recently it has been shown by our group that β2M expressed highly in blood samples of old people comparing to youngers. Furthermore, we have shown that β2M correlated significantly with oxidative stress biomarkers, which could underscore a potential role in oxidative stress network. Therefore, there is a rationality to test the expression of β2M across different group of age using other easier source of sample such as buccal cells.
Buccal cells are epithelial cells that are similar to brain and skin in nature. Buccal cells can be collected easily, deriving a high number of cells that can be used for different biological assays. Comparing to other sample methods, buccal cell samples are less invasive and very easy to collect. In addition, buccal cells are very stable after isolation from the mouth, which makes them easy to process and analyze. Moreover, buccal cells are easy to preserve, making them an easy source for diagnosis.
In this study, we used buccal cells to examine the expression of β2M in different age groups. The expression of β2M increased significantly with fold change 3.40, 4.80, 6.60, 8.20 and 12.04 for the group of age 18-25 years, 26-35 years, 36-45 years, 46-55 years, and 56-70 years respectively. The same observation was seen with markers of biological aging (p16INK4a) with fold change 3.19, 3.90, 4.80, 8.50 and 12.40 for the group of age 18-25 years, 26-35 years, 36-45 years, 46-55 years, and 56-70 years respectively.
As expected, there was an increase in expression of inflammatory genes (IL-1β and IL-6) in the elderly. Moreover, there was a direct significant correlation (Pearson correlation coefficient, r = 90) between β2M expression and age, and the same direct significant correlation between p16INK4a expression and age was also seen (r = 90). In addition, a direct correlation between β2M and p16INK4a was also seen (r = 0.83), there was also direct correlation between β2M and IL-1β (r = 0.5) and IL-6 (r = 0.68).
This evidence showed that β2M increased in buccal cells of the elderly compared to younger, and thereby buccal cells can be exploited to assess biological aging by measuring β2M levels, however, large sample size and using another assessing method such as β2M protein levels should be performed to confirm the results.