Mutated Stem Cells in Our Bone Marrow Associated with Disease and Mortality
When we think of mutated cells, some of us think of monsters. Some of us may think about cancer. But did you know that we all have mutated cells cruising around our bodies every day? Let me explain.
Defining Mutated Cells
A mutated cell occurs when the genetic sequence that makes up that cell becomes permanently altered in some way. These mutations can be hereditary (genetic) or they can be somatic (acquired). Inherited mutations are present before birth and throughout life, and these mutations can be passed on to the next generation.
Somatic mutations, on the other hand, are acquired at some point during the person’s life, perhaps due to constant overexposure to the sun, chemicals, or smoking for example. Some of these cells are so dysfunctional that they can’t function normally nor can they divide and replicate. A few do grow and divide, so the genetic mutation is passed on to the cloned cells that are created within that person. While mutations can cause diseases, such as cancer, your body is constantly identifying these cells and taking them out by attacking them.
Our feature study today focuses on these somatic mutations in the hematologic system and the conditions in which these mutations are associated.
The Hematologic System and Hematopoiesis
The hematologic system consists of blood and blood-producing tissues (e.g., bone marrow) as well as immune cells, so hematologic conditions would include leukemias, myelomas, and lymphomas for example. Another term you need to be familiar with is hematopoiesis, which is the process of blood cell (red, white, and platelets) production by hematopoietic stem cells in the bone marrow.
Your Risk of Mutated Cells May Increase as You Age
While cell mutations are understood to exist in those with hematologic disorders (cancer, for example, would be a result of the activation of these mutations), the new study set out to determine if these somatic (acquired) cell mutations were common in those without hematologic disorders.
DNA analysis of blood cells determined those subjects who had no inherited risk for (or who weren’t genetically prone to) hematologic diseases. The 160 genes that are known to be mutated in hematologic cancers were analyzed in the subjects without genetic risk. The results? While somatic mutations were rare in those under age 40, this significantly increased with aging as evidenced by the following results:
- Age 60–69: 5.6% had somatic mutations
- Age 70–79: 9.5% had somatic mutations
- Age 80–89: 11.7% had somatic mutations
- Age 90–108: 18.4% had somatic mutations
In these subjects, somatic mutations in the hematopoietic stem cells (the blood-producing cells) of bone marrow were not only associated with an increased risk of hematologic cancers with aging but also with all-cause mortality (death from any cause), heart disease, and stroke. These somatic mutations are found in bone marrow and blood cells, and this finding (predisease) on blood screening, for example, actually has a term: clonal hematopoiesis of indeterminate potential, or CHIP for short. In other words, somatic mutations (as evidenced by the detection of CHIP) in hematopoietic stem cells and the conditions associated with these mutations—cancer, heart disease, stroke, and more—increase as you age and are associated with your risk of death. The more of these abnormal cells, the more likely it is that you will die from a plethora of diseases.
The upshot? If confirmed by other studies, this is a VERY big discovery. Why? While we’re busy as doctors chasing cholesterol and other blood level or serum markers, the percentage of your cells that have mutated may turn out to be a far more important indicator of your overall health and risk of dying. If that’s the case, then your cumulative exposure to things like radiation, the sun, chemicals, electromagnetic fields, and the like may be an important metric that determines your health. On the other hand, we all have robust cellular machinery to repair these cell mutations. In people that live to be 100, it’s been noted that their cell repair mechanism doesn’t get degraded as much as they age. Hence, finding ways to keep that cell repair machinery revved up may be the next wonder drug, regardless of exposure levels!