{"id":37,"date":"2023-05-23T19:14:46","date_gmt":"2023-05-23T23:14:46","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=37"},"modified":"2026-05-27T13:37:43","modified_gmt":"2026-05-27T17:37:43","slug":"section-1-neoplasia","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/section-1-neoplasia\/","title":{"raw":"Review of Cell Cycling, DNA duplication, Cell Differentiation and Errors that can lead to Cancer","rendered":"Review of Cell Cycling, DNA duplication, Cell Differentiation and Errors that can lead to Cancer"},"content":{"raw":"

Review of Cell Cycling, Cell Division, and DNA duplication<\/strong><\/h3>\r\n[caption id=\"attachment_6063\" align=\"alignnone\" width=\"258\"]\"\"<\/a> Cell Division[\/caption]\r\n\r\nCell cycling <\/strong>and cell division<\/strong> in humans begins during embryonic development, starting with the fertilized oocyte (zygote).\u00a0 Undoubtedly you don't remember when you were this young, however, your first act as a zygote was to grow larger in size and then divide from one cell into two identical cells.\u00a0 This process is termed cell cycling.<\/strong>\u00a0 During cell cycling in somatic cells, the cell becomes larger, duplicates its organelles and DNA and then divides into two identical daughter cells.\u00a0 This process of somatic cell duplication is sometimes called cell division<\/strong>, or cell proliferation<\/strong> or simply mitosis.<\/strong>\r\n\r\n \r\n\r\n[caption id=\"attachment_5764\" align=\"alignnone\" width=\"300\"]\"First<\/a> First Mitotic Event. The first mitotic event (termed cleavage) occurs after the oocyte is fertilized. In this process the zygote undergoes each stage of the cell cycle - growth, DNA duplication, and cytokinesis, resulting in the production of two identical daughter cells. These daughter cells continue to undergo cell cycling to produce a ball of cells which will eventually develop into an embryo.[\/caption]\r\n\r\nThe steps of cell cycling are all equally important. The process begins in interphase<\/strong> and there are three distinct stages within interphase: G1<\/sub>, S<\/strong>, and G2<\/sub>.<\/strong>\u00a0 In G1,<\/strong> the cell is grows in size and duplicates its organelles.\u00a0 In S phase<\/strong>, DNA duplication occurs and in G2<\/sub>,<\/strong> the cell grows a bit more.\u00a0 Enzymes check DNA for errors during duplication, triggering either repair<\/strong> or apoptosis<\/strong> if mutations<\/strong> are found.\u00a0 After these 3 phases of interphase are complete, the cell enters mitosis.<\/strong>\u00a0 Within mitosis, the enlarged cell proceeds through four phases: prophase, metaphase, anaphase<\/strong> and telophase,<\/strong> finally dividing into two cells during cytokinesis,<\/strong> with half of its organelles and one full set of DNA (23 pairs of chromosomes) ending up in each daughter cell.\r\n\r\n[caption id=\"attachment_2405\" align=\"alignnone\" width=\"300\"]\"Cell<\/a> Cell Cycle: A cell moves through a series of phases in an orderly manner. During interphase, G1 involves cell growth and protein synthesis, the S phase involves DNA replication and the replication of the centrosome, and G2 involves further growth and protein synthesis. The mitotic phase follows interphase. Mitosis is nuclear division during which duplicated chromosomes are segregated and distributed into daughter nuclei. Usually the cell will divide after mitosis in a process called cytokinesis in which the cytoplasm is divided and two daughter cells are formed.[\/caption]\r\n\r\n[caption id=\"attachment_2404\" align=\"alignnone\" width=\"300\"]\"Animal<\/a> Animal cell mitosis is divided into five stages\u2014prophase, prometaphase, metaphase, anaphase, and telophase\u2014visualized here by light microscopy with fluorescence. Mitosis is usually accompanied by cytokinesis, shown here by a transmission electron microscope. (credit \u201cdiagrams\u201d: modification of work by Mariana Ruiz Villareal; credit \u201cmitosis micrographs\u201d: modification of work by Roy van Heesbeen; credit \u201ccytokinesis micrograph\u201d: modification of work by the Wadsworth Center, NY State Department of Health; donated to the Wikimedia foundation; scale-bar data from Matt Russell)[\/caption]\r\n

Review of Cell Differentiation<\/strong><\/h3>\r\nDuring embryonic development through the process of mitosis, a ball of cells called a blastocyst is created.\u00a0 At this point in time cells have begun to mature and differentiate<\/strong> to forming an inner cell mass<\/strong> which will differentiated into three unique cell lineages (endoderm, mesoderm,<\/strong> and ectoderm)<\/strong> in a process called gastrulation.<\/strong>\u00a0 Within each of these cell types, cells continue to undergo cell cycling and the embryo gets larger and larger in total size.\u00a0 Eventually these cells will become even further differentiated forming lineages for all 200 cell types of the human body (e.g. epithelial cells, cardiomyocytes, hepatocytes, etc.).\r\n\r\n[caption id=\"attachment_6065\" align=\"alignnone\" width=\"210\"]\"Totipotent<\/a> Totipotent embryonic stem cells (e.g., zygote and morula cells) are capable of developing into every cell type of a fully functioning embryo as well as the extra-embryonic tissues (e.g., placenta). There are three types of pluripotent stem cells (the endoderm, mesoderm and ectoderm lines) and they make up the cells of the inner cell mass of the blastocyst embryo. The endoderm line gives rise to the nervous tissue and skin. The mesoderm cells differentiate into muscle, bone and blood. The endoderm develops into the lungs and digestive organs. Multipotent stem cells are undifferentiated cells capable of dividing and differentiating into closely related cell types within specific tissues. Multipotent stem cells enable the replacement of old, dsyfunctional, or damaged cells in the body.[\/caption]\r\n\r\nOrgans will form with unique sets of these cell types becoming more functional.\u00a0 Within each organ and tissue, some daughter cells (termed stem cells<\/strong>) continue to cell cycle, producing more cells, allowing the embryo to get larger.\u00a0 After each round of mitosis, many daughter cells exit<\/strong> the cell cycle, entering the G0<\/sub> phase<\/strong> and full mature (differentiate).\u00a0 Cells that become fully mature can usually no longer cell cycle and divide, and instead express specific proteins and enzymes to provide functionality to the organ or tissue that they are part of.\u00a0 This process of growth and maturation continues through all stages of development from embryo to fetus to newborn to child to teenager.\u00a0 Even as a full-size adult, many tissues contain stem cells that divide in order to allow for the replacement of mature cells that get old and die.\u00a0 At adulthood, most cells have exited the cell cycle and have fully differentiated to ensure that each organ and tissue is functional. Depending on the conditions, cells that do exit the cell cycle and enter G0<\/sub><\/strong> can enter a state of reversible inactivity (quiescent), irreversible inactivity<\/strong> (senescent),<\/strong> or differentiation (maturation).<\/strong> At adulthood, most cells have exited the cell cycle and have fully differentiated to ensure that each organ and tissue is functional.\r\n\r\n[caption id=\"attachment_2406\" align=\"alignnone\" width=\"300\"]\"Cells<\/a> Cell Cycling Regulation - Exiting of Cell Cycle to Enter Quiescent (Inactive) Stage, G0: Cells that are not actively preparing to divide enter an alternate phase called G0. In some cases, this is a temporary condition until triggered to enter G1. In other cases, the cell will remain in G0 permanently.[\/caption]\r\n\r\n \r\n

What are Telomeres?<\/strong>\r\nTelomeres <\/strong>are the end caps of chromosomes, and they shorten with each cell division, which is thought to act as a safety net to limit the number of rounds of cell cycling that is possible.\u00a0 Telomere shortening<\/strong> helps prevent excessive divisions, as each time DNA is duplicated the possibility of DNA errors and mutations increases.\u00a0 Limiting the number of times a cell undergoes DNA duplication and mitosis therefore reduces the risk of mutations.\u00a0 Once telomeres reach a certain length, apoptosis is triggered, preventing further cell division and potential cancerous growth.\u00a0 DNA mutations<\/strong> are the first step<\/strong><\/span> of cancer development.<\/strong><\/p>\r\n\r\n

DNA mutations are the first step of Cancer Development<\/strong><\/h3>\r\nUnfortunately, during the cell cycle\u2019s S phase, as DNA is duplicated, there is a chance for DNA errors<\/strong> to occur as nucleotides (adenine, thymine, guanine, cytosine) are strung together by DNA polymerases.\u00a0 Luckily there are several enzymes that check the DNA for errors during duplication<\/strong> that will trigger apoptosis<\/strong> if mutations<\/strong> are found that cannot be fixed. It is known that mutations that occur in DNA (depending on the location in the DNA) can cause cancer. It is also known that inevitably DNA errors do occur during duplication just due to the sheer number of times DNA is duplicated, not to mention the number of nucleotides within each of the 23 pairs of chromosomes (which include ~3 billion base pairs all together). It may seem obvious that the more DNA duplication events there are, the more risk there is for DNA errors to occur. Therefore, a person's age<\/strong> becomes a risk factor for the development of cancer.\u00a0 Additionally, one can also imagine that if any of the enzymes<\/strong> responsible for checking DNA for errors<\/strong> in S phase are damaged or mutated or absent, that again person has an increased risk of accumulating mutations and therefore are susceptible to developing cancer.\r\n\r\n[caption id=\"attachment_313\" align=\"alignnone\" width=\"300\"]\"\"<\/a> The skin is comprised of 3 main layers: the epidermis, dermis and subcutaneous fat. UV light from the sun can penetrate the skin and damage DNA in the nucleus of skin cells. If the cells are not able to repair this damage, or repair it improperly, it can lead to uncontrolled cell growth and formation of a tumor. A tumor is considered cancerous when it is able to metastasize, or grow outside of its normal tissue. Developing skin cancer is more likely to happen with more or more frequent sun exposure, sunburns, or with age, as the cells lose their ability to repair DNA because there is too much or too repeated damage. Wearing sunscreen can help shield your skin cells from UV light and can help prevent skin cancer[\/caption]\r\n\r\n \r\n

The Role of Telomeres and Telomerase Re-Activation in Cancer<\/strong><\/h3>\r\nTelomeres,<\/strong> the end caps of chromosomes are maintained through childhood and adolescence through the enzymatic action of telomerase,<\/strong> an enzyme which continues to add telomere to the ends of chromosome. Telomerase is inactivated<\/strong> in adulthood, and the telomeres begin to shorten with each cell division, acting as a safety net to limit the number of cell divisions possible. At a certain length, a critical point is reached, and the cell becomes inactive (senescent)<\/strong> or dies.<\/strong> This telomere shortening helps prevent excessive divisions, reducing the risk of mutations and cancer development. Additionally, at a certain age the cell has likely become less functional or dysfunctional,<\/strong> potentially accumulating waste products or abnormalities<\/strong> and it would become detrimental<\/strong> to the body if it wasn't inactivated or removed. In tissue that is regenerative, old cells can be replaced through the division of tissue-specific stem cells. In cells that die when telomeres reach a certain length, apoptosis is triggered and macrophages<\/strong> engulf and recycle the cellular components. Interestingly it has been found that in 90% of cancers, telomerase has been re-activated<\/strong> in the cancerous cells (which unfortunately helps the cancer cells to become immortal<\/strong> - continually adding telomere length and thereby permitting continual cell cycling).\r\n\r\n[caption id=\"attachment_5836\" align=\"alignnone\" width=\"300\"]\"Figure.<\/a> Figure. Telomere shortening with every cell division paradoxically provides both protection and also contributes to aging related tissue degeneration. When telomeres reach a critical length, the cells enter senescence or undergo apoptosis. This provides protection from the accumulation of genetic errors though also is linked to tissue degradation. It has been found that Chronic Inflammation and Oxidative Stress, depicted by an increase in free radicals (e.g., Reactive Oxygen Species, ROS) can lead to cellular and DNA damage DNA and telomere shortening. Antioxidants (e.g., vitamins C and E, and polyphenols) neutralize free radicals, reducing telomeric attrition. Similarly, anti-inflammatory agents (e.g., omega-3 fatty acids) as well as statins have been found to reduce inflammation and telomeric attrition.[\/caption]\r\n

The Roles of Telomerase Inhibitors and Activators in Future Possible Therapies for Cancer and Aging Respectively<\/strong><\/h3>\r\n[caption id=\"attachment_5830\" align=\"alignnone\" width=\"300\"]\"\"<\/a> Possible future anti-cancer and anti-aging therapies:\u00a0 a) Telomerase inhibitors could prevent telomerase from becoming reactivated and therefore help prevent cells from maintaining long telomeres and becoming immortal cancer cells. b) and c) Assuming cells are still protected by p53 activity, Senolytics and Telomerase Activators could potentially be used to inhibit telomere shortening which may contribute to premature aging.[\/caption]\r\n\r\nPossible future cancer therapies could involve using Telomerase Inhibitors<\/strong> to block the reactivation of telomerase that can occur in cancer cells.\u00a0 Telomerase<\/strong> is an enzyme that is normally inactivated in most adult cells, aside from those cells that need to divide regularly (e.g., certain adult stem cells). Telomerase lengthens telomeres which can contribute to cell immortality.\u00a0 In these possible future therapies, it is important to consider p53<\/strong> which is called the Guardian of the Genome<\/strong>. p53 is a tumor suppressor gene<\/strong>, that codes for an enzyme that activates DNA repair<\/strong> and stops the cell cycle at the G1\/S cell cycle checkpoint<\/strong> to allow time for DNA repair to occur.\u00a0 Additionally, p53 will initiate apoptosis<\/strong> if DNA damage is beyond repair.\u00a0 Furthermore, p53 also plays an essential role in cells becoming senescent<\/strong> when telomeres shorten to a specific length. Cells that have a loss of p53 expression or mutations in p53 are therefore at risk for developing DNA mutations and becoming cancerous.\r\n\r\nAs indicated in the above figure, future anti-cancer<\/strong> therapeutic Telomerase Inhibitors<\/strong> would prevent telomerase from becoming reactivated and therefore help prevent cells from maintaining long telomeres and becoming immortal cancer cells.\u00a0 Also, assuming cells are still protected by p53 activity, future anti-aging<\/strong> therapeutic Senolytics<\/strong> and Telomerase Activators<\/strong> could potentially be used to inhibit telomere shortening which may have been stimulated by processes that lead to premature aging.","rendered":"

Review of Cell Cycling, Cell Division, and DNA duplication<\/strong><\/h3>\n
\"\"<\/a>
Cell Division<\/figcaption><\/figure>\n

Cell cycling <\/strong>and cell division<\/strong> in humans begins during embryonic development, starting with the fertilized oocyte (zygote).\u00a0 Undoubtedly you don’t remember when you were this young, however, your first act as a zygote was to grow larger in size and then divide from one cell into two identical cells.\u00a0 This process is termed cell cycling.<\/strong>\u00a0 During cell cycling in somatic cells, the cell becomes larger, duplicates its organelles and DNA and then divides into two identical daughter cells.\u00a0 This process of somatic cell duplication is sometimes called cell division<\/strong>, or cell proliferation<\/strong> or simply mitosis.<\/strong><\/p>\n

 <\/p>\n

\"First<\/a>
First Mitotic Event. The first mitotic event (termed cleavage) occurs after the oocyte is fertilized. In this process the zygote undergoes each stage of the cell cycle – growth, DNA duplication, and cytokinesis, resulting in the production of two identical daughter cells. These daughter cells continue to undergo cell cycling to produce a ball of cells which will eventually develop into an embryo.<\/figcaption><\/figure>\n

The steps of cell cycling are all equally important. The process begins in interphase<\/strong> and there are three distinct stages within interphase: G1<\/sub>, S<\/strong>, and G2<\/sub>.<\/strong>\u00a0 In G1,<\/strong> the cell is grows in size and duplicates its organelles.\u00a0 In S phase<\/strong>, DNA duplication occurs and in G2<\/sub>,<\/strong> the cell grows a bit more.\u00a0 Enzymes check DNA for errors during duplication, triggering either repair<\/strong> or apoptosis<\/strong> if mutations<\/strong> are found.\u00a0 After these 3 phases of interphase are complete, the cell enters mitosis.<\/strong>\u00a0 Within mitosis, the enlarged cell proceeds through four phases: prophase, metaphase, anaphase<\/strong> and telophase,<\/strong> finally dividing into two cells during cytokinesis,<\/strong> with half of its organelles and one full set of DNA (23 pairs of chromosomes) ending up in each daughter cell.<\/p>\n

\"Cell<\/a>
Cell Cycle: A cell moves through a series of phases in an orderly manner. During interphase, G1 involves cell growth and protein synthesis, the S phase involves DNA replication and the replication of the centrosome, and G2 involves further growth and protein synthesis. The mitotic phase follows interphase. Mitosis is nuclear division during which duplicated chromosomes are segregated and distributed into daughter nuclei. Usually the cell will divide after mitosis in a process called cytokinesis in which the cytoplasm is divided and two daughter cells are formed.<\/figcaption><\/figure>\n
\"Animal<\/a>
Animal cell mitosis is divided into five stages\u2014prophase, prometaphase, metaphase, anaphase, and telophase\u2014visualized here by light microscopy with fluorescence. Mitosis is usually accompanied by cytokinesis, shown here by a transmission electron microscope. (credit \u201cdiagrams\u201d: modification of work by Mariana Ruiz Villareal; credit \u201cmitosis micrographs\u201d: modification of work by Roy van Heesbeen; credit \u201ccytokinesis micrograph\u201d: modification of work by the Wadsworth Center, NY State Department of Health; donated to the Wikimedia foundation; scale-bar data from Matt Russell)<\/figcaption><\/figure>\n

Review of Cell Differentiation<\/strong><\/h3>\n

During embryonic development through the process of mitosis, a ball of cells called a blastocyst is created.\u00a0 At this point in time cells have begun to mature and differentiate<\/strong> to forming an inner cell mass<\/strong> which will differentiated into three unique cell lineages (endoderm, mesoderm,<\/strong> and ectoderm)<\/strong> in a process called gastrulation.<\/strong>\u00a0 Within each of these cell types, cells continue to undergo cell cycling and the embryo gets larger and larger in total size.\u00a0 Eventually these cells will become even further differentiated forming lineages for all 200 cell types of the human body (e.g. epithelial cells, cardiomyocytes, hepatocytes, etc.).<\/p>\n

\"Totipotent<\/a>
Totipotent embryonic stem cells (e.g., zygote and morula cells) are capable of developing into every cell type of a fully functioning embryo as well as the extra-embryonic tissues (e.g., placenta). There are three types of pluripotent stem cells (the endoderm, mesoderm and ectoderm lines) and they make up the cells of the inner cell mass of the blastocyst embryo. The endoderm line gives rise to the nervous tissue and skin. The mesoderm cells differentiate into muscle, bone and blood. The endoderm develops into the lungs and digestive organs. Multipotent stem cells are undifferentiated cells capable of dividing and differentiating into closely related cell types within specific tissues. Multipotent stem cells enable the replacement of old, dsyfunctional, or damaged cells in the body.<\/figcaption><\/figure>\n

Organs will form with unique sets of these cell types becoming more functional.\u00a0 Within each organ and tissue, some daughter cells (termed stem cells<\/strong>) continue to cell cycle, producing more cells, allowing the embryo to get larger.\u00a0 After each round of mitosis, many daughter cells exit<\/strong> the cell cycle, entering the G0<\/sub> phase<\/strong> and full mature (differentiate).\u00a0 Cells that become fully mature can usually no longer cell cycle and divide, and instead express specific proteins and enzymes to provide functionality to the organ or tissue that they are part of.\u00a0 This process of growth and maturation continues through all stages of development from embryo to fetus to newborn to child to teenager.\u00a0 Even as a full-size adult, many tissues contain stem cells that divide in order to allow for the replacement of mature cells that get old and die.\u00a0 At adulthood, most cells have exited the cell cycle and have fully differentiated to ensure that each organ and tissue is functional. Depending on the conditions, cells that do exit the cell cycle and enter G0<\/sub><\/strong> can enter a state of reversible inactivity (quiescent), irreversible inactivity<\/strong> (senescent),<\/strong> or differentiation (maturation).<\/strong> At adulthood, most cells have exited the cell cycle and have fully differentiated to ensure that each organ and tissue is functional.<\/p>\n

\"Cells<\/a>
Cell Cycling Regulation – Exiting of Cell Cycle to Enter Quiescent (Inactive) Stage, G0: Cells that are not actively preparing to divide enter an alternate phase called G0. In some cases, this is a temporary condition until triggered to enter G1. In other cases, the cell will remain in G0 permanently.<\/figcaption><\/figure>\n

 <\/p>\n

What are Telomeres?<\/strong>
\nTelomeres <\/strong>are the end caps of chromosomes, and they shorten with each cell division, which is thought to act as a safety net to limit the number of rounds of cell cycling that is possible.\u00a0 Telomere shortening<\/strong> helps prevent excessive divisions, as each time DNA is duplicated the possibility of DNA errors and mutations increases.\u00a0 Limiting the number of times a cell undergoes DNA duplication and mitosis therefore reduces the risk of mutations.\u00a0 Once telomeres reach a certain length, apoptosis is triggered, preventing further cell division and potential cancerous growth.\u00a0 DNA mutations<\/strong> are the first step<\/strong><\/span> of cancer development.<\/strong><\/p>\n

DNA mutations are the first step of Cancer Development<\/strong><\/h3>\n

Unfortunately, during the cell cycle\u2019s S phase, as DNA is duplicated, there is a chance for DNA errors<\/strong> to occur as nucleotides (adenine, thymine, guanine, cytosine) are strung together by DNA polymerases.\u00a0 Luckily there are several enzymes that check the DNA for errors during duplication<\/strong> that will trigger apoptosis<\/strong> if mutations<\/strong> are found that cannot be fixed. It is known that mutations that occur in DNA (depending on the location in the DNA) can cause cancer. It is also known that inevitably DNA errors do occur during duplication just due to the sheer number of times DNA is duplicated, not to mention the number of nucleotides within each of the 23 pairs of chromosomes (which include ~3 billion base pairs all together). It may seem obvious that the more DNA duplication events there are, the more risk there is for DNA errors to occur. Therefore, a person’s age<\/strong> becomes a risk factor for the development of cancer.\u00a0 Additionally, one can also imagine that if any of the enzymes<\/strong> responsible for checking DNA for errors<\/strong> in S phase are damaged or mutated or absent, that again person has an increased risk of accumulating mutations and therefore are susceptible to developing cancer.<\/p>\n

\"\"<\/a>
The skin is comprised of 3 main layers: the epidermis, dermis and subcutaneous fat. UV light from the sun can penetrate the skin and damage DNA in the nucleus of skin cells. If the cells are not able to repair this damage, or repair it improperly, it can lead to uncontrolled cell growth and formation of a tumor. A tumor is considered cancerous when it is able to metastasize, or grow outside of its normal tissue. Developing skin cancer is more likely to happen with more or more frequent sun exposure, sunburns, or with age, as the cells lose their ability to repair DNA because there is too much or too repeated damage. Wearing sunscreen can help shield your skin cells from UV light and can help prevent skin cancer<\/figcaption><\/figure>\n

 <\/p>\n

The Role of Telomeres and Telomerase Re-Activation in Cancer<\/strong><\/h3>\n

Telomeres,<\/strong> the end caps of chromosomes are maintained through childhood and adolescence through the enzymatic action of telomerase,<\/strong> an enzyme which continues to add telomere to the ends of chromosome. Telomerase is inactivated<\/strong> in adulthood, and the telomeres begin to shorten with each cell division, acting as a safety net to limit the number of cell divisions possible. At a certain length, a critical point is reached, and the cell becomes inactive (senescent)<\/strong> or dies.<\/strong> This telomere shortening helps prevent excessive divisions, reducing the risk of mutations and cancer development. Additionally, at a certain age the cell has likely become less functional or dysfunctional,<\/strong> potentially accumulating waste products or abnormalities<\/strong> and it would become detrimental<\/strong> to the body if it wasn’t inactivated or removed. In tissue that is regenerative, old cells can be replaced through the division of tissue-specific stem cells. In cells that die when telomeres reach a certain length, apoptosis is triggered and macrophages<\/strong> engulf and recycle the cellular components. Interestingly it has been found that in 90% of cancers, telomerase has been re-activated<\/strong> in the cancerous cells (which unfortunately helps the cancer cells to become immortal<\/strong> – continually adding telomere length and thereby permitting continual cell cycling).<\/p>\n

\"Figure.<\/a>
Figure. Telomere shortening with every cell division paradoxically provides both protection and also contributes to aging related tissue degeneration. When telomeres reach a critical length, the cells enter senescence or undergo apoptosis. This provides protection from the accumulation of genetic errors though also is linked to tissue degradation. It has been found that Chronic Inflammation and Oxidative Stress, depicted by an increase in free radicals (e.g., Reactive Oxygen Species, ROS) can lead to cellular and DNA damage DNA and telomere shortening. Antioxidants (e.g., vitamins C and E, and polyphenols) neutralize free radicals, reducing telomeric attrition. Similarly, anti-inflammatory agents (e.g., omega-3 fatty acids) as well as statins have been found to reduce inflammation and telomeric attrition.<\/figcaption><\/figure>\n

The Roles of Telomerase Inhibitors and Activators in Future Possible Therapies for Cancer and Aging Respectively<\/strong><\/h3>\n
\"\"<\/a>
Possible future anti-cancer and anti-aging therapies:\u00a0 a) Telomerase inhibitors could prevent telomerase from becoming reactivated and therefore help prevent cells from maintaining long telomeres and becoming immortal cancer cells. b) and c) Assuming cells are still protected by p53 activity, Senolytics and Telomerase Activators could potentially be used to inhibit telomere shortening which may contribute to premature aging.<\/figcaption><\/figure>\n

Possible future cancer therapies could involve using Telomerase Inhibitors<\/strong> to block the reactivation of telomerase that can occur in cancer cells.\u00a0 Telomerase<\/strong> is an enzyme that is normally inactivated in most adult cells, aside from those cells that need to divide regularly (e.g., certain adult stem cells). Telomerase lengthens telomeres which can contribute to cell immortality.\u00a0 In these possible future therapies, it is important to consider p53<\/strong> which is called the Guardian of the Genome<\/strong>. p53 is a tumor suppressor gene<\/strong>, that codes for an enzyme that activates DNA repair<\/strong> and stops the cell cycle at the G1\/S cell cycle checkpoint<\/strong> to allow time for DNA repair to occur.\u00a0 Additionally, p53 will initiate apoptosis<\/strong> if DNA damage is beyond repair.\u00a0 Furthermore, p53 also plays an essential role in cells becoming senescent<\/strong> when telomeres shorten to a specific length. Cells that have a loss of p53 expression or mutations in p53 are therefore at risk for developing DNA mutations and becoming cancerous.<\/p>\n

As indicated in the above figure, future anti-cancer<\/strong> therapeutic Telomerase Inhibitors<\/strong> would prevent telomerase from becoming reactivated and therefore help prevent cells from maintaining long telomeres and becoming immortal cancer cells.\u00a0 Also, assuming cells are still protected by p53 activity, future anti-aging<\/strong> therapeutic Senolytics<\/strong> and Telomerase Activators<\/strong> could potentially be used to inhibit telomere shortening which may have been stimulated by processes that lead to premature aging.<\/p>\n

Media Attributions<\/h2>