It is believed that the major changes in the genome that lead to cancer arise from mutations in tumor suppressor genes.
[7] In genetic knock-out and rescue experiments, restoration of a caretaker gene from the mutated form to the wildtype version does not limit tumorigenesis.
[12] In many cases, gatekeeper genes encode a system of checks and balances that monitor cell division and death.
[4] When tissue damage occurs, for example, products of gatekeeper genes ensure that balance of cell growth over cellular death remains in check.
[17] Biochemical cascades consisting of signaling proteins occur in the ECM and play an important role to the regulation of many aspects of cell life.
Because mechanisms that control the accumulation of damage through the lifetime of a cell are essential to longevity, it is logical that caretaker and gatekeeper genes play a significant role in cellular aging.
[19] It is believed that degradation of telomeres, the ends of chromosomes, through repeated cell cycle divisions, is a main component of cellular aging and death.
It has been suggested that gatekeeper genes confer beneficial anti-cancer affects but may provide deleterious effects that increase aging.
As the organism ages, however, these formerly beneficial pathways become deleterious by inducing apoptosis in cells of renewable tissues, causing degeneration of the structure.
[18] For example, defects in nucleotide excision repair pathways are associated with premature aging phenotypes in diseases such as Xeroderma pigmentosum and Trichothiodystrophy.
These patients exhibit brittle hair, nails, scaly skin, and hearing loss – characteristics associated with simple human aging.
Geneticists studying these premature-aging syndromes propose that caretaker genes that determine cell fate also play a significant role in aging.
Experiments with mice that have increased gatekeeper function in the p53 gene show reduced cancer incidence (due to the protective activities of products encoded by p53) but a faster rate of aging.
[18] It has been proposed that mutations in gatekeeper genes could, to an extent, offer a sort of selective advantage to the individual in which the change occurs.
[11] Caretaker genes, on the other hand, confer selective disadvantage because the result is inherently decreased cellular success.
In many cases, gatekeeper genes encode a system of checks and balances that monitor cell division and death.
[4] In cases of tissue damage, for example, gatekeeper genes would ensure that balance of cell growth over cellular death remains in check.
Mutations that occur within these cell lineages remain confined to the compartment in which they reside, increasing the future risk of cancer.
[4] This is also protective, however, because the cancer will remain confined to that specific area, rather than invading the rest of the body, a phenomenon known as metastasis.
In areas of the body compartmentalized into small subsets of cells, mutations that lead to cancer most often begin with caretaker genes.
[4] On the other hand, cancer progression in non-compartmentalized or large cell populations may be a result of initial mutations in gatekeepers.