There is ‘liminal space’ between cellular life and death. Despite the fact that they are often thought of as oxymoronic, it is not as straightforward. Many have grappled to denote the moment of death for humans: Is it when the beating of the heart no longer occurs? When breathing stops? A lack of detectable activity? Divergent answers arise as death is a process, and by definition, not an irreversible one.
In regard to cells, predominantly it is assumed that once the cells pass critical checkpoints, the death process is irrevocable. Such checkpoints include condensation of nucleus, collapse of DNA, disintegration of the mitochondria and cell shrinkage. Moreover, these events are often intentional. An essential component of life is programmed cell death, with over 20 forms proposed. Among these, apoptosis is the most notable and well-studied due to its regulatory mechanisms in cell suicide, and crucial roles in embryonic development, maintaining a balance of cellular multiplication and regulating internal conditions (homeostasis) by eradicating the undesired, faulty or dangerous cells in the body.
Apoptosis in Greek is defined as ‘falling’ and it expedites the habitual turnover of cells, analogous to leaves falling from a tree in autumn. A number of triggers are involved in apoptosis, but at length they activate a decisive group of ‘executioner’ proteins named caspases. These enzymes, by cleaving hundreds of various types of proteins within a cell, inflict destruction in cellular targets, attack structural proteins and deconstruct the cytoskeleton, resulting in cell shrinkage to blebs and die.
With all this, dubiety also follows. The fence which segregates life and death is porous even at the degree of cells (the rudimentary units of life). A growing body of evidence have recently demonstrated that cells that are believed to be dead or terminal are able to revive themselves, or somewhat revive, hence reverse apoptosis when under the right conditions. This phenomenon is referred to as anastasis (Greek for ‘rising to life’) and can occur in vitro and in vivo.
A significant role that anastasis plays involves the maintenance of differentiated cells that are difficult to recoup, such as neurons and cardiomyocytes. In this way, anastasis can counter many of the complications resulted by apoptosis. A variety of degenerative diseases, such as Alzheimer and Parkinson, are associated with apoptosis not functioning correctly. This is because protein aggregation can activate an enzyme that triggers apoptosis, resulting in the death of neurons and loss of brain function.
However, if we rival apoptosis to the demolition of buildings, the detrimental effects that arise when anastasis takes place can be also understood. The caspases involved in the breakdown of cellular structures are somewhat like demolition workers destroying buildings. If someone decides after: “I don’t want it to be destroyed, please rebuild it.” Then, the damage has to be repaired, but this process of restoring may go wrong. You won’t have a complete replica of the original. Therefore, when anastasis takes place, the resurrected cells may bear chromosomal abnormalities and acquire mutations. This will engender a multiplier effect where particular mutations will cause unchecked cell growth and proliferation. Henceforth, this revival process may trigger normal cells to become carcinogenic, by gaining new mutations and transmuting into more hostile and metastatic cancers. In this way, cancer cells are said to employ anastasis as a way to ‘cheat death’ and use it as an escape tactic to survive cell- death- inducing anti-cancer therapy (e.g. chemotherapy and radiotherapy).
The correlation between anastasis and cell regeneration, rise of disorders and cell death decision is yet to be elucidated, as additional research is required to confirm a direct link. Ultimately, if there truly is a correlation, the resurrection of cells could increase awareness into multidisciplinary fields of science that supplement our understanding in the control of cell survival and destruction. Furthermore, it could provide insight into identifying novel analeptic approaches for brain damage, cancer, injury to tissue and moreover regeneration medicine by meditating the reversibility of apoptosis.
1. Kroemer G, et al. 2009. Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009
2. Jacobson MD, Weil M, Raff MC. 1997. Programmed cell death in animal development.
3. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. 2002. The cell cycle and programmed cell death.
4. Burke PJ. 2017. Mitochondria, bioenergetics and apoptosis in cancer.
5. Tang HL, et al. 2012. Cell survival, DNA damage, and oncogenic transformation after a transient and reversible apoptotic response.
6. Tang HL, Yuen KL, Tang HM, Fung MC. 2009. Reversibility of apoptosis in cancer cells.
7. Taylor RC, Cullen SP, Martin SJ. 2008. Apoptosis: controlled demolition at the cellular level.
8. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
9. Sun G, Guzman E, Balasanyan V, Conner CM, Wong K, Zhou HR, et al. A molecular signature for anastasis, recovery from the brink of apoptotic cell death
10. Tang HL, Tang HM, Fung MC, Hardwick JM. In vivo Caspase Tracker biosensor system for detecting anastasis and non-apoptotic caspase activity.
11. Baskar R, Lee KA, Yeo R, Yeoh K-W. Cancer and radiation therapy: current advances and future directions.
By Gaya, Year 11