Anything related to the word ‘death’ generally has a negative connotation. However, in the context of cell death, is death really bad? Cell death is in fact, an essential and natural process crucial for maintaining your body’s homeostasis and overall health, playing a protective role rather than causing harm.
There are many ways that cells can sacrifice themselves for the good of the whole organism, and one of the key mechanisms that is critical to health is called programmed cell death. “Programmed” means that your body knows these cells are damaged and need to be eliminated. So, it manages the process of cell death from start to finish.
‘Apoptosis’ is a form of programmed cell death that happens when a cell incurs damage from senescence, stress, or injury. Apoptosis does not trigger an inflammatory response. It is a tightly regulated process that removes damaged cells, preventing them from developing into tumors caused by DNA damage that leads to uncontrolled cell division. It also avoids triggering unnecessary inflammation, which can result in symptoms like fever, swelling, redness, or pain. This process occurs daily, particularly in tissues like the skin, which is constantly exposed to UV radiation, pollution, physical abrasion, and microbial contact, necessitating a continuous renewal process to maintain its protective functions.
Apoptosis can be triggered by two main pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is activated when cells experience internal stress, such as DNA damage or nutrient deprivation. Such stress causes mitochondria to release proteins that initiate a chain reaction leading to cell death. The extrinsic pathway starts when external signals, like Fas ligand, bind to its receptor on the surface of a cell. This binding triggers a chain reaction inside the cell that leads to apoptosis. The Fas receptor is found on many types of cells, while Fas ligand is mainly found on activated T cells. These T cells use Fas ligand to kill target cells and also to regulate their own numbers through a process called activation-induced cell death (AICD). However, some tumor cells exploit this pathway by producing Fas ligands themselves. This allows them to trigger apoptosis in T cells, protecting the tumor from immune attack and making it more difficult for the body to eliminate the cancer.
What happens if apoptosis fails to remove damaged cells? Beyond the risk of tumor formation, another consequence is the development of autoimmune conditions such as lupus. When apoptosis doesn’t eliminate overly active immune cells, these cells can attack the body’s own tissues, leading to autoimmune disorders. Another example of faulty apoptosis is ‘endometriosis’, a debilitating condition where uterine tissue grows excessively. When apoptosis fails, this tissue is not properly regulated, leading to uncontrolled growth, pain, and other complications.
Another form of programmed cell death occurs through the process of autophagy, derived from the Greek word for “self-eating”. Autophagic cell death clears out damaged cells to regenerate newer, healthier ones by recycling components from the damaged cells, removing harmful substances from outside the cell to promote health and longevity. Methods that trigger autophagy include fasting, a ketogenic diet, and exercise. Fasting is the most effective method to trigger autophagy as it forces the body to alter its energy source from glucose to fat. Although there is no direct evidence that links autophagy to weight loss, research has shown that autophagy may reduce appetite and thus indirectly support weigh loss.
Autophagy is a tightly regulated process that is regarded as the waste management or housekeeping system of the cell. Disrupted autophagy has been associated with conditions such as diabetes, neurodegenerative disorders, and certain cancers. In Alzheimer’s disease, for example, impaired autophagy affects immune cells in the brain called microglia, making them less effective at clearing harmful protein clumps. These protein clumps then trigger an overreaction in microglia, which begin to attack neurons and contribute to the progression of the disease. However, these harmful effects can be reduced by using drugs that boost autophagy.
While autophagy is generally beneficial for maintaining cellular health, excessive activation of this process may pose risks. For instance, research indicates that overactive autophagy can lead to the death of cardiac cells, potentially contributing to heart failure. Additionally, while autophagy may protect against cancer in some cases, certain cancer cells can exploit autophagy to support their survival and growth. Further studies are needed to better understand the complex relationship between autophagy and cancer, as well as its broader implications for health and disease.
Programmed cell death is a vital process that protects and maintains your health. Your cells are always ready to sacrifice themselves for the greater good. Truly, cell death is one of the unsung heroes keeping you alive.
Tianning Yu
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