Understanding the cell cycle and cellular senescence is crucial in unraveling the mysteries of how cells divide and age. Cells grow, change and age while they fulfill their functions within our bodies, greatly in part due to the happenings of the cell cycle. A cell grows continuously and spends most of its time in interphase, which is subdivided into the G₁, S, G₂, and M phases. During these phases, the cell will replicate its DNA, duplicate its organelles, and eventually mitotically divide to produce an identical daughter cell. Throughout the cell cycle, there are certain checkpoints to ensure there are favorable internal and external conditions to the cell before committing to the extensive process of replication and division¹.

A cell may be delayed in a specialized resting state, known as G₀, if environmental factors are unfavorable. The amount of time spent in the G₀ rest phase depends on the cell type, function and resource availability and may be categorized as reversible or irreversible. A cell in a reversible state is said to be quiescent and may re-enter the cell cycle once activated. In an irreversible state the cell may either be differentiated or senescent. A differentiated cell would be a stem cell that has asymmetrically divided into a specialized cell that stays in a G₀ state while performing their functions indefinitely. Conversely, a senescent cell is permanently removed from the cell cycle and can no longer replicate and will remain in this state until the cell’s death². Considering this, cellular senescence is a subcategorization of the G₀ checkpoint in which the cell is removed from the cell cycle differing only in the state of permanence.

Cellular senescence is an occurrence defined by the cessation of cell division in response to a multitude of reasons, including telomere damage, oxidative stress, mitochondrial and DNA dysfunction^3,4. The depletion of stem cells and cellular senescence are part of the normal cell ageing process. Additionally, senescence serves as a cancer deterrent in that a cell that is expressing abnormal qualities is removed from the cell cycle at the G₀ checkpoint, is not allowed to duplicate and may undergo apoptosis⁴.

Shifting gears to DNA promoter regions, let’s explore how these regions influence gene expression in cells. A promoter region is defined as an upstream region of DNA that tells transcription factors where to bind and initiate the transcription of a certain gene to produce an RNA molecule⁵. A mutation or alteration in the sequence of a promoter region’s base pairs may lead to a cryptic promoter region. Cryptic promoters differ from regular DNA promoter regions in that they are hidden or unexpected sequences within the DNA that can mistakenly activate gene expression. On the other hand, regular DNA promoter regions are the usual sites where transcription factors bind to initiate the transcription of specific genes in a controlled and predictable manner⁶. Cryptic transcription differs from normal DNA transcription in that it involves the activation of genes by unregulated look-alike promoter sequences in the DNA, leading to gene expression in an abnormal or unintended manner that interferes with normal cellular processes⁷.

References

1. Alberts, B., Johnson, A., Lewis, J., et al. Molecular Biology of the Cell. 2002; National Library of Medicine, https://www.ncbi.nlm.nih.gov/books/NBK26869/.
2. Wikipedia contributors. G0 phase 2024; https://en.wikipedia.org/wiki/G0_phase#:~:text=The%20G0%20phase%20describes,of%20as%20a%20resting%20phase.
3. Wikipedia contributors. Cellular senescence 2024; https://en.wikipedia.org/wiki/Cellular_senescence#cite_note-1.
4. McHugh, D., Gil, J. Senescence and aging: Causes, consequences, and therapeutic avenues. J Cell Biol. 2018; 217,1: 65-77
5. Segre, J. Promoter. 2024; National Human Genome Research Institute, https://www.genome.gov/genetics-glossary/Promoter#:~:text=Definition&text=A%20promoter%2C%20as%20related%20to,molecule%20(such%20as%20mRNA).
6. Pattenden, S., Gogol, M., Workman, J. Features of Cryptic Promoters and Their Varied Reliance on Bromodomain-Containing Factors. 2010; National Library of Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2944879/.
7. Shalchi, H. Cryptic transcription in mammalian stem cells linked to aging. 2021; Baylor College of Medicine, https://www.bcm.edu/news/cryptic-transcription-in-mammalian-stem-cells-linked-to-aging.