On page 185-186, Dr. Moalem defines the Hayflick Limit and terms Leonard Hayflick as “one of the fathers of modern aging research”. The Hayflicks limit, in simple terms, is the maximum number of times a cell may divide in the human body. The Hayflicks limit relates to Big Idea 2 (Biological systems utilize free energy and molecular building blocks to grow, to reproduce and to maintain dynamic homeostasis) because it deals with cell division. Since Hayflick’s research was done in the 1960s, find additional research that has been done on the Hayflick limit, and describe an experiment that has used the Hayflick limit. Also, on page 186, Dr. Moalem uses an example to help simplify the Hayflick limit. Come up with your own example and describe it thoroughly.
The Hayflicks limit is related to the development of cancer, however, research and find out if there is any other disease affected by the Hayflicks limit.
The Hayflick Limit, named for Dr. Leonard Hayflick (1928-present), is the number of times that a normal cell can replicate before undergoing apoptosis and dying. According to Dr. Moalem, the Hayflick Limit in humans is somewhere from “fifty-two to sixty” (185). The reason for the existence of the Hayflick Limit is telomeres, protective ends of DNA that shorten with each cell replication. It is these ends that are quintessential to understanding cancer proliferation: cancerous cells employ the enzyme telomerase to lengthen the telomeres, allowing the cell to exceed the Hayflick Limit and evade apoptosis.
ReplyDeleteThe Hayflick Limit was discovered in 1961 at the Wistar Institute in Philadelphia. Since then, more research has been done to better understand the Hayflick Limit and its practical implications, primarily in the discipline of oncology – the study of cancer. In a journal article1 published on August 29, 2012 in PLOS ONE (published by the Public Library of Science), the Hayflick Limit was investigated in a non-human context: this particular study focused on the Tasmanian Devil, the “world’s largest carnivorous mammal” (1). Specifically, this study sought to understand the proliferation tactics of Devil Facial Tumor Disease (DFTD), a “unique clonal cancer” (1), which threatens to render the animal extinct.
DFTD spreads through oral contact during biting, which is a normal part of social interaction between Tasmanian Devils; the disease is often fatal within six months of infection, causing rapid organ failure. Prior studies into this disease have concluded that, like most cancer cells, cells infected with DFTD use telomerase to repair their telomeres, avoiding the senescence that somatic cells normally face. The study sought to measure the lengths of telomeres, telomere location, telomere replication number, and other telomere-related data in order to better understand the correlation between telomeres and the Hayflick Limit for this particular disease.
This study found that telomeres have a very significant effect on a cell’s ability to surpass the Hayflick Limit. Through analysis of multiple samples from multiple different animals of multiple organs from multiple geographic locations (within the island of Tasmania, south of Australia), several conclusions were drawn. First, not only are telomeres important, DFTD cells actively regulate the length of their telomeres. Shorter telomeres (length unspecified) are elongated by telomerase while longer telomeres are protected from further elongation by a shelterin complex. This conclusion was drawn from the presence of TINF2 (TERF1-interacting nuclear force 2), a protein known to engage in negative regulation of telomerase activity (negative regulation is where an increase in the concentration of a substance directly results in a decrease in the concentration of that same substance). Secondly, telomerase activity was shown to allow the cell to circumvent certain cell cycle checkpoints that check for faulty or defunct telomeres; exactly how this circumvention is accomplished is yet to be discovered.
Overall, the journal article referred to above furthers biological knowledge surrounding the usurpation of the Hayflick Limit, specifically as it pertains to telomeres, telomerase, and cancerous cells. From this, Leonard Hayflick’s discovery of the maximum reproduction number can be extended to explain why many cancer cells demonstrate increased levels of fitness: telomerase activity, heavy in cancerous cells, prevents the usual apoptosis signal from being generated, resulting in unparalleled cellular reproduction in excess of the Hayflick Limit.
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ReplyDeleteOn page 186, Dr. Moalem uses an analogy of copying a manuscript at Kinko’s to explain telomeres and the Hayflick Limit. However, as a math geek, I like to think about things from a mathematical standpoint. The way I think about telomeres and the Hayflick Limit is like this: you have a multiplication problem to perform, but it’s extremely long and thus it is easy to mistype something into your calculator, so you recruit your entire math class to perform the problem so that the validity of your answer can be assured. However, each subsequent person is given a modified form of the function: the first and last numbers are removed, leaving an expression with two fewer numbers. The Hayflick Limit would be the number of numbers you have to multiply: if the problem were 7*5*2*12*6*18*424, then the Hayflick Limit would be 7. However, in order to ensure that everybody gets the same answer, you add a bunch of 1s onto the end: 1*1*1*1*7*5*2*12*6*18*424*1*1*1*1. This way, until you reach the ‘chromosome’ (the actual expression whose value is sought), everybody gets the same answer even with the removal of the 1s from the end; the 1s are the metaphorical telomeres.
The Hayflick Limit might also be instrumental in understanding the effects of HIV (human immunodeficiency virus) on the Helper-T Cells that play crucial roles in the human Immune System. According to a journal article2 published in Mechanisms of Ageing and Development, cells infected with HIV reflect healthy cells that are reaching the Hayflick Limit: old and non-proliferative, susceptible to disease. The difference, however, is that the cells infected with HIV are often nowhere near the Hayflick Limit, but the result is the same: increased susceptibility to invading pathogens leads to more frequent sickness and eventually death. As such, understanding the mechanisms behind the Hayflick Limit – how cells know to self-destruct when their telomeres are shortened, from a biochemical standpoint – can help us to better understand how to combat the deadly precursor to AIDS (acquired immunodeficiency syndrome).
1Ujvari, Beata, Anne-Maree Pearse, and Robyn Taylor. "Telomere Dynamics and
Homeostasis in a Transmissible." PLOS ONE 7.8 (2012): 1-8. EBSCOhost. Web.
1 Apr. 2013. .
2 Effros, Rita B. "Impact of the Hayflick Limit on T cell responses to infection:
lessons from aging and HIV disease." ["doi:10.1016/j.mad.2003.11.003"].
Mechanisms of Ageing and Development 125.2 (2004): 103-06. NCBI. Web. 1
Apr. 2013. .
(Justin Millman, jmillma4@students.d125.org)
[for above two: sorry, the superscript and citations didn't format properly]
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