Is Multiple Sclerosis Linked to Accelerated Aging at the Cellular Level?

Multiple sclerosis (MS) is a complex disease that affects the central nervous system. While it's known that both genetic and environmental factors play a role, a new study is exploring the connection between MS and the aging process at a cellular level. Specifically, researchers are investigating whether people with MS show signs of accelerated biological aging in their immune cells.

What is Epigenetic Age Acceleration?
Our bodies change as we get older. But these changes aren't just chronological; they can also be biological. Epigenetics, which refers to heritable and modifiable mechanisms of genetic regulation, can be used to measure a person’s biological age. One way to measure this is through DNA methylation (DNAm), which is the addition of a methyl group to a DNA nucleotide. DNAm patterns change as we age and can be used to estimate biological age using what are called "epigenetic clocks".

The difference between a person's biological age, as determined by these clocks, and their actual chronological age, is called epigenetic age acceleration (EAA). This EAA has been linked to various health issues. The study used the GrimAge clock, which is considered the most accurate in predicting mortality. The GrimAge clock uses DNAm-based markers for plasma proteins and smoking history.

Key Findings of the Study
* Overall Accelerated Aging in MS: The study found that, overall, people with MS showed a statistically significant increase in EAA compared to those without MS. The MS group's epigenetic age was about 9 months more accelerated than the control group.

* B Cells are Key: When looking at different types of immune cells, researchers discovered that the accelerated aging was mainly found in B cells. This was particularly noticeable in a validation analysis of data from isolated B cells, which showed an average EAA increase of over 5 years in MS patients. In contrast, T cells did not show any signs of EAA in people with MS.

* Beta-2-Microglobulin and Smoking: The study also identified specific factors that seem to be contributing to this accelerated aging. Specifically, the DNAm markers for beta-2-microglobulin (B2M) and smoking history (measured in pack-years) were significant contributors to EAA in the B cells of people with MS. B2M is involved in immune system function, while smoking is a known contributor to many age-related diseases.

* Gender Differences: The study confirmed that men tend to have higher EAA than women. However, they also noted that women with MS showed higher EAA than women without MS.

What Does This Mean?
The fact that B cells, which are important in the immune system, are showing signs of accelerated aging in MS patients suggests that this may contribute to the disease. It’s hypothesized that premature B-cell aging, or immunosenescence, might play a role in MS. Age-associated B cells (ABCs) are more likely to secrete pro-inflammatory cytokines and autoantibodies, potentially contributing to the autoimmune nature of MS.

Additionally, the study's findings regarding B2M and smoking are important because these are factors that can be influenced. B2M is a protein associated with immune function and inflammation. The study showed that DNAm surrogates for B2M and smoking both strongly correlated with the EAA of B-cells.

Looking Ahead
This study offers compelling evidence for a link between biological aging and MS, specifically implicating B cells. It emphasizes the need for future research focusing on age-related mechanisms in B cells and how these mechanisms could be targeted to treat MS. Future studies will also need to assess how treatments affect EAA and whether this may help slow disease progression. More longitudinal studies are needed to fully understand how EAA changes over time, how it is affected by treatment, and how it correlates with disease progression.

In conclusion, this study contributes to a better understanding of the underlying mechanisms of MS and provides new avenues of research to help improve the lives of people living with the disease.

Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

Reference:
Maltby, V., Xavier, A., Ewing, E., Campagna, M. P., Sampangi, S., Scott, R. J., ... & Lechner-Scott, J. (2023). Evaluation of cell-specific epigenetic age acceleration in people with multiple sclerosis. Neurology, 101(7), e679-e689.