  |
|
|
|
The body has developed various means to protect itself against cancer, tumor-suppressors being an important mechanism. Tumor-suppressors are genes that can be stimulated to produce proteins that carry out functions to protect the body against cancer. Tumor-suppressors can be categorized into caretaker and gatekeeper proteins. Caretaker proteins act to prevent or repair genomic (DNA) damage to the cell. Gatekeeper proteins inhibit the propagation of potential cancer cells by arresting their growth (cellular senescence), or by inducing their death by the process of apoptosis.
Since tumor-suppressors act by curtailing the development of malignant tumors, it stands to reason that they should promote longevity by preventing premature death. This is indeed the case, but we will want to consider the all the factors that influence longevity in addition to cancer. Recent studies support the role of caretaker proteins in promoting longevity by non-cancer prevention means as well. The studies show that certain defects in the DNA-repair pathways due to loss of caretaker function are associated with an increase in the rate in which specific characteristics of ageing develop. However, recent evidence indicates that the gatekeeper mechanisms of apoptosis and cellular senescence can dually suppress the development of cancer and promote the development of specific ageing characteristics. Why should tumor suppression lead to an increase in the ageing process? There are two main hypotheses to account for the phenomenon of ageing. The first hypothesis states that ageing is due to damage to the cells by oxidation. Free radicals are highly reactive species that promote rapid oxidation as an inevitable product of body metabolic processes. The body has a limited capacity to disactivate free radicals before they do their damage. The second hypothesis, known as antagonistic pleiotrophy, may have particular relevance for the action of tumor suppressors. This hypothesis, based on evolution, holds that ageing is a consequence of the declining force of natural selection. The early history of man was characterized by a hostile environment in which most individuals died at an early age. Survival of the species required the selection of genes that supported the health and fitness of young individuals, while there were very few older individuals alive that would exhibit detrimental traits to which selection pressure could be applied. How do tumor-suppressor proteins perform their function? The two main tumor-suppressors are p53 and retinoblastoma (RB) proteins. p53 and RB are active in two tumor suppressor pathways that interact and regulate each other. Since cancer is characterized by the hyperactivity of the cell cycle and excessive cell division, these two proteins act by arresting the cell cycle. p53 levels increase in response to DNA damage to the cell, and stimulate certain genes to produce proteins that halt the cell cycle. If p53 or the genes that it activates cannot correct the DNA damage, the cell receives signals to undergo apoptosis, or programmed cell death. The regulated manner of apoptosis ensures that cells die and are removed by scavenging cells without the release of destructive enzymes or triggering inflammatory responses that occur when cells die by other means. RB protein acts more directly on the cell cycle, leading to cell senescence or apoptosis. Go To Page: 1 2
The copyright of the article Do Tumor-Suppressors Promote Ageing? in Cancer Treatment is owned by David Olle. Permission to republish Do Tumor-Suppressors Promote Ageing? in print or online must be granted by the author in writing.
|
|
|
|
