¶ … Cellular Function and Aging
Tumor Suppression Protein 53 and Effects on Cellular Function and Aging
The concept of aging has many intrinsic and extrinsic factors that act as markers on an individual organism. Ignoring mortality associated with external environmental factors, very few organisms can be said to have cellular immortality with no decrease in cellular function or repeat division in normal diploid cells. Cellular senescence is a normal process that halts cellular division after a set of cycles of replication. Senescent cells can remain completely functional but lose the programmed process of replication. The normal pathway for senescent cells is either aging with metabolic pathways continuing for the cell or programmed cell death which is known as apoptosis that occurs when cellular function changes, a specific lifetime is reached for the cell or the cell is damaged. The multicellular cnidarians known as a Hydra has been shown to have a complete lack of senescence in cellular function with cells dividing frequently and continuously and being sloughed off at the tips of appendages and new stem cells continuously repopulating (Watanabe 2009). The hydra organism effectively shows no aging (Martinez 1998) and studies of the Hydra genome show that the organism has a mutation in the expression of the p53 gene that manifests as a lack of p53 protein in hydra cells (Rutkowski 2010). The link between a lack of p53 expression and aging has been studied exhaustively with the inverse relationship between tumor suppression and cell immortality at balance with the expression of the protein. What has not been studied under such significant scrutiny has been the relationship between p53 expression and cellular senescence which is the halting of cellular processes to form a dormant cell. The tradeoff for having no pathway to halt cellular activity is continuous cell division and replenishment which the hydra has exploited to live an immortal life. For a more complex animal with differentiated organ systems the nature of p53 tumor suppression and "immortality" is a legitimate tradeoff between insuring that cancer cells become dormant and undergo apoptosis (programmed cell death) and renewing the organ systems of the body.
A recent publication titled Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor by Jean Phillippe Coppe etal observes the relationship between the byproducts of cells that have been made senescent (dormant) and the healthy cells surrounding them. The results of the research in the paper show that human cells induced into senescence by the suppression of the p53 tumor suppression protein and the upregulation of oncogenic RAS secrete proteins that are both toxic and can lead to expression of cancer in normal cells surrounding the senescent ones. Aging is dependent on the rate of cellular regeneration throughout all of a person's organs. As the rate of regeneration slows and cells either die off or are induced into senescence, organs age. At the surface, it appears that halting apoptosis and cellular senescence would be a ticket to immortality similar to the hydra; this immortality is short lived as dampening pathways to cellular senescence and apoptosis leads to the development of cancers brought on by DNA damage or other mutations (Lowe 2003). Senescence appears to be an important mechanism for decreasing the capability of cancer cells to multiply and divide; if cells with DNA damage or malignant tendencies can be turned off and placed in a "holding pattern" then the effect should be beneficial to the organism. A paradox is apparent when both the capability to regenerate new cells and the potential for secreting damaging molecules occurs through the very mechanism designed to protect an organism from developing cancer. This tug-of-war is termed antagonistic pleiotropy and is the heart of the relationship balancing cancer prevention and aging where each is both beneficial and inversely proportional to the other (Kirkwood 2000).
Senescence as a cellular state is a fairly broad definition; however the specific pathology is an inactivation of the cell's ability to divide while still maintaining metabolic function. The cell may or may not continue to function with the original processes within tissue but specific behaviors, pathways and secretions continue to occur with senescent cells and these cells can have effects on surrounding cells. Research has shown that the number of senescent cells in mammalian tissue increases with increasing age (Campisi 2005) Researchers studying aging and possible solutions to slow the effects of the process have focused attention on p53 function and senescent cells. The "Catch 22" associated with inhibiting p53 and increases in cancer or...
Tumor Suppression Protein 53 and Effects on Cellular Function and Aging Tumor Suppression Protein 53 (P53) was originally linked to tumor proliferation and thought to be an oncogene. Research led to an understanding that P53 was in actuality a tumor suppression protein and suppression of the P52 gene is the most widely genetic defect found in tumors (Levine 1991). Further study of p53 and the family of tumor suppression genes led
Tumor Suppressor p53 The p53 tumor suppressor, also known as the TP 53 or tumor protein can be referred to as a gene that codes for a protein that is responsible for the regulation of the cycle of the cell and therefore acting as tumor suppression. It is significant for cells in multicellular organisms to suppress cancer, p53 has been referred to as ‘the guardian of the genome’ as extracted from
Efforts to Achieve Healthy Aging Ping-Chung Leung Institute of Chinese Medicine, The Chinese University of Hong Kong, HKSAR. Abstract: Longevity is a blessing as long as good health is not lost. However, the tendency to have a decline on normal physiological activities is inevitable because of the natural processes of degeneration at all levels: molecular, cellular and organic. Hence, the elderly people frequently suffer from cardiovascular problems and skeletal deteriorations that gradually develop
Prostate cancer is a type of cancer that develops in the male reproductive system, and most prostate cancer can be slow growing. However, there are still aggressive type of prostate cancers, because the cancer cells can spread from the prostate of a patient to all other part of the body particularly the lymph nodes and bones. Initially, prostate cancer may reveal no symptom, however, in a later stage, it can
Chocolate: Behind Its Bad Rap In today's society, chocolate is everywhere. It seems that people have developed a love-hate relationship with chocolate. According to the U.S. Department of Commerce, in 1997, the average American ate 11.7 pounds of chocolate. American adults ranked chocolate as the most-craved food and as their favorite flavor by a three-to-one margin. (Mustad, 2001) Throughout the world, exists a society of chocolate lovers. While Americans consume, on average,
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