Introduction
The word senescent generally means an irreversible biological process of arresting the ability of the cells to multiply and perform efficiently. Here in senescent bone marrow, the entire cellular cycle of the bone marrow has been put to stop. This scenario occurs as an aging process where the cells of the bone marrow cause alteration in the production of red blood cells. This process of senescence is also seen in other parts of the body, along with the bone marrow. Although the senescence of bone marrow cells affects both the stromal (connective tissue cells) and the hematopoietic (blood-forming) cells equally, the effect it has on the hematopoietic cells is comparatively greater as it shows a drastic reduction in cellular production.
What Is a Tumor Microenvironment?
The microenvironment of a tumor is the viable area or ecosystem surrounding the body of the tumor, which provides a source of nutritional supply for the tumor to grow. The cellular matrix (cell components) of the microenvironment includes the extracellular matrix (a closely packed network of various large cellular molecules in a particular manner), immune cells, and other blood cells like fibroblasts. Here, the tumor cells show both positive and negative influences on the microenvironment. Having an understanding of the microenvironment of the tumor gives an insight into the tumor behavior, the pattern of cellular growth, its multiplication, and the structures supplying it. Scientists claim that the particles of the microenvironment associate with each other and also with the tumor, enabling the growth of the cancer cells.
What Is a Bone Marrow Microenvironment?
The microenvironment of the bone marrow is considered the domicile or home of the blood-forming stem cells, along with the cancer cells growing in that area. These changes in the bone marrow microenvironment are influenced by several complex interactions with the physiology of the blood-forming hematopoietic cells. However, these interactions of the bone marrow along with the other cells near it are also seen in the cell physiology and growth of blood-related cancers.
What Are the Conditions Seen Associated With Bone Marrow Senescent?
Senescence as a phenomenon is commonly associated with elderly people as it is often associated with the progression of the disease. The senescent of bone marrow disorders are often seen as associated with clinical conditions like the following:
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Myeloproliferative Neoplasm (MPN) - The myeloproliferative neoplasm or MPN is a cancer of the bone marrow that produces the blood cells. During this condition, there are evident alterations in the production of new blood cells, including white blood cells, red blood cells, and platelets that are abnormal in size, shape, and structure.
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Leukemia - Leukemia is the cancer of the cells of the lymphatic system and bone marrow, which produce cells of the blood.
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Multiple Myeloma - Multiple myeloma is a rare type of blood cancer that primarily affects the plasma and white blood cells. In this disease, an increase in cell proliferation is commonly seen.
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Myelodysplastic Syndrome - As the name myelodysplastic syndrome suggests, the condition is seen involving multiple types of cancers that involve immature blood cells present in the bone marrow.
What Is the Mechanism of Bone Marrow Senescent?
The senescence of the cell is an irreversible process where the cellular proliferation is limited or stopped. This mechanism is triggered in association with factors like chemokines, proteases, proinflammatory cytokines, and growth factors, where this concept of association of these factors with senescence is known as SASP (senescence-associated secretory phenotype). The condition begins as the body’s response to cell damage suppresses the growth of cancer cells, accelerates tissue repair, and promotes wound healing. The external factors also act as triggering agents to induce senescence, and they include,
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Oxidative Stress - It occurs as a disturbance amidst the balance of the production of free radicals and defensive antioxidants fighting against it.
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Radiation - This is the emission of potential cell-damaging electromagnetic waves, done in a very targeted, controlled approach at a specific site in a given amount of time.
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DNA Damage - The damage to the DNA refers to the alteration in the physical or chemical properties of DNA, leading to mutation of the cells or a disruption in normal cell functions.
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Cytotoxic Chemotherapy - This procedure is a type of cancer treatment where a chemotherapeutic drug is specifically used to ascertain the death of the tumor cells, thus rapidly declining the growth of cancer.
This mechanism of scenes is mediated by an enzyme called the cyclin-dependent kinase inhibitor p21 and p16, which are seen in conditions like retinoblastoma and P53 as a tumor suppressor. There is also a visible activation of the tumor suppressor pathway that prevents the cell cycle from progressing and gradually leading to a cell-regulated coordinated cell death called apoptosis.
What Are the Conditions That Trigger Bone Marrow Senescence?
The conditions that predispose to bone marrow senescence are:
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Senescence of Bone Marrow Aging - Bone marrow is the primary site for blood cell production, including the long and flat bones; the blood cells are differentiated into the rate of maturity, types, and site of production. As aging progresses, there is a simultaneous alteration in the cells of the bone marrow, significantly making the blood cell components stand apart from the fat cells. The impact of bone marrow senescence impacts the immune system of the body.
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Senescence Due to Clonal Hematopoiesis - The age factor plays an important role in the scene of clonal hematopoiesis, where the accumulation of genetic factors determines the cell's life. There is an increased level of cell mutation in the premature cells of the same genetic type. While this may not be causing symptoms by itself, this condition can actively be a precursor for various other health conditions like cardiovascular diseases, blood cancer, etc.
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Senescence Accelerated Due to Chemotherapy - Chemotherapy is the procedure in which higher-dose cytotoxic antibiotics are used to contain the growth of the tumor cells. This, in turn, affects the bone marrow, creating a senescence limiting the proliferation of new blood cells.
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Senescence Seen in the Tumor Microenvironment - The senescence seen in the tumor environment can be a very interesting factor as it limits the growth and progression of the tumor cells. This phenomenon is achieved by the senescence-associated secretory phenotype (SASP), which produces reactive protein components like chemokines, cytokines, growth factors, matrix remodeling factors, etc.
Conclusion
As discussed above, the senescence of bone marrow is a very crucial factor, as it plays important roles in both cell production and tumor growth. As bone marrow has the highest potential to produce blood cells, so does the senescence prevent the growth of the tumor cells. This is coordinated by various factors in the body, which all together contribute to the cessation of cell growth. Senescence, especially in cases of cancers, can be greatly helpful and is the most sought outcome for cancer treatments. Many treatment modalities, like chemotherapy, radiation, etc., cohesively aim to achieve this. However, the senescence of bone marrow cells should also be under a controlled watch in order to overrule the emergency of any new clinical conditions.
