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Expansion, structure reform
I'm considering adopting the following as the base arrangement:
- 1. Cellular senescence
- 2. Organismal senescence
- 3. Effects
- 4. Hypotheses
- 5. Treatment
- 6. Differences between taxa
- 7. Evolution
- 8. Accelerated aging-disorders
- 9. Cloning
Senescence / Senesce
Can anyone explain the difference between Senescence & Senesce. Is senesce an actual word. It is mentioned once in the article and can be found else where on the net. Are they used interchangeably? Ctbolt (talk) 04:49, 9 August 2013 (UTC)
Protein Misfolding Theory of Aging
I would like to add the following section to this page. As a biochemistry professor who has studied human aging for 35 years, I am currently beginning a clinical trial on this cause of aging. I have previously worked on slowing the other processes, and think this practical information is likely to greatly reduce human suffering by reducing the development of chronic disease. OR ELSe it could be entered as a separate new article, just linked on the senescence page as 3.7 Rocordman (talk) 20:36, 23 November 2014 (UTC)
Contents [hide] 3.7 Protein Misfolding or Translational Error Theory of Aging 3.7.1 The free radical theory of aging 3.7.2 Inflammation 3.7.3 Telomere shortening 3.7.4 Translational infidelity error theory of aging 3.7.5 Teaberry Trial
Protein Misfolding or Translational Error Theory of Aging The Translational Error Theory of human aging –“Lost in Translation”
There are many theories about why humans age, what causes chronic diseases to develop, and why we eventually die. Below four are highlighted which one can clearly do something about. Understanding the rationale and evidence for each of these theories provides guidance on actions one can take that help increase healthspan. Healthspan is the term used to distinguish lifespan or years of being alive, from years of aging in a pleasant state of health. Most people want their years to be enjoyable, and not a burden for those who care about them. Below are theories of aging for which specific actions can be taken easily.
The free radical theory of aging This theory is well documented. To lessen free radical damage, I consume vitamin C 500 mg twice a day, vitamin E 400IU twice a week, and eat a diet of colorful fruits and vegetables that contain a variety of antioxidants.
Inflammation Also called “Inflammaging” by researchers, this is a cause of chronic disease, including plaque in the arteries, cancer, etc. To reduce inflammation, I consume fish oil, avoid 4-legged meat, reduce stress by exercising and avoiding the media, by treasuring friends, meditating and doing yoga.
Telomere shortening The length of telomeres, which are caps on the end of the DNA in our cells, preserve our genetic information to allow longevity. Actions that shorten telomeres include stress and high metabolic rate. Consuming antioxidants, staying fit, and relaxing are all useful to keep long telomeres. Note that EGCG and quercetin help maintain telomere length .
Translational infidelity error theory of aging The basic mechanism is that mRNA is translated incorrectly, incorporating the wrong amino acids into proteins that then fold improperly (based on the AA error theory of Wolfgang Freist). These proteins are either destroyed, causing a shortage of needed proteins, or worse, remain malfunctioning and accumulating as hazardous waste such as plaque in Alzheimer’s. Processes that will lessen functional proteins being lost in translation include: 1) increasing the availability of needed amino acids, 2) slowing the rate of translation to increase accuracy, 3) providing time for better proofreading, 4) increasing degradation of misfolded proteins, or 5) diluting the accumulated damage by half through cell division. Helpful actions include getting exercise, eating blueberries, drinking green tea, and adjusting the diet to include beneficial foods, such as tomatoes, onions, strawberries, and cabbage. Protein misfolding and translation errors have been documented as a cause of human aging .
One hypothesis of a major cause of aging is errors in translation. One source of such errors is caused by incorrect binding of amino acids of similar structure to tRNA that are then misincorporated into proteins, which subsequently do not function properly. Another possibility is when translation occurs so rapidly that proteins are not properly proofread or do not fold into the proper three dimensional structure.
The first place errors can occur is when the amino acid (AA) is bound to the transfer RNA. Briefly, deficiency of three AAs (PHE, SER, and GLN) (PSG) and excess of 2 AAs (CYS and MET) (CM) increase the occurrence of errors, so correct protein sequences are lost in translation. For human evidence, a metabolomics study was done of 100 yr old Italians. They had high levels of PSG in their blood, which may have reflected that they ate foods containing high levels of PSG.
One can search for foods that are particularly rich in PSG, and have less CM. A group of Italians living past 100 were probably eating a Mediterranean diet, which is known to be far superior to the Western diet, and also is high in PSG and low in CM
This paragraph explains why those 5 AAs are so important. For instance, phenylalanine (PHE), an essential aromatic AA, is similar in structure to tyrosine and tryptophan, and when the PHE-tRNA should bind PHE, the wrong AA might be incorporated. So by ensuring there is enough PHE available, this mistake is less likely to occur. The Italian centenarian results suggest this type of error is especially likely for three AAs, PSG, so eating a diet with foods containing more of these is likely to reduce such errors. CYS and MET are 2 AAs that contain highly reactive –SH groups that are likely to crosslink and be oxidized by free radicals. –SH is also likely to bind Al, Cu, and Fe. Those metal atoms generate lots of free radicals, and are suspected to contribute to Alzheimer’s and Parkinson’s diseases.
The second likely source of protein errors is when protein synthesis is too rapid. There are proofreading mechanisms that will catch mistakes as the protein is being synthesized, if translation is going slowly enough. One way to slow the process is by exercising. This depletes the supply of ATP, which is necessary to synthesize proteins. After exercise, your proteins are more likely to be synthesized slowly, allowing proper proofreading so mistakes can be corrected. Another molecule that slows translation is EGCG EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells . Green tea has much higher levels of EGCG than black tea or other foods. The abundant polyphenols from blueberries such as quercetin help prevent the degradation of EGCG. So eating blueberries, and drinking a single cup of green tea will raise EGCG levels 4 to 8 fold . The EGCG inhibits myosin motors running the cell, slowing key processes that might otherwisse cut short effective proofreading. This may be a key reason that green tea is well known to increase longevity. Healthspan has been shown to increase regularly up to 5 cups of green tea daily . Combined with eating blueberries, only one or two cups of green tea may be needed.
Finally, after the protein is made, there may be further checkpoints. Chaperone proteins exist in our bodies to ensure that proteins fold into the proper shape. If they do not fold properly, usually they are degraded by a structure known as the proteasome. However, some mistakes escape this process, especially ones that act as prions. After bacteria and then viruses were discovered, the next disease-causing contagious particles to be discovered were infectious proteins, known as prions. These proteins are improperly folded, and they cause other proteins to misfold as well. An example is the degenerative brain disease scrapie. There is concern that eating brain material from animals that had this disease will cause the disease in other animals, and probably even humans. It is possible Alzheimer’s is a disease of this nature, where plaque in the brain may be caused by beta-amyloid, a misfolded protein that coagulates and then cannot be degraded by proteasomes.
Once we are adults, cell division is rare, so misfolded proteins that are not degraded will accumulate. It is likely this is especially damaging for proteins that adhere to chromosomal DNA causing errors in gene expression that can cause cancer. Those proteins on chromosomes are often not repaired. However, during mitosis the cell divides so faulty proteins are diluted from one cell to two. So newly divided cells, including stem cells, stay much healthier than “senescent” cells that no longer divide.
Dr. Martin is arranging internet-based studies that can be completed at home to determine whether food choices, including consumption of blueberries and green tea, may be able to partially reverse damage caused by the accumulation of misfolded proteins and deficiency of proper folding. Senescent cells with adequate levels of polyphenols and EGCG may continue to degrade misfolded proteins and produce functional ones, and such recovery may be measurable by tests of abilities like memory that can be conducted online. To receive email notices when such trials have been authorized, please email Roc Ordman at email@example.com, SUBJ: Healthspan trial.
Here is an index of healthspan activities.
Teaberry Trial The Teaberry Trial is a clinical trial to develop a nutraceutical method to reduce the risk for what may be a major cause of human aging, or senecense, and the development of chronic disease. For other efforts, see Strategies for Engineered Negligible Senescence. The trial has been approved by the Beloit College IRB, is being managed by Roc Ordman, and analyzed by Rolf Martin. Professor Ordman, nicknamed Nutrition Investigator , is interested in extending human healthspan. The goal of Nutrition Investigator is to help people achieve the maximum healthspan based on current nutrition research. Here is current information to extend healthspan with convenient actions. The first key to the Teaberry Trial is the health benefits of blueberries. This is based on results of a clinical trial since 2002. The benefits found from this trial for which Rolf Martin has been responsible for analysis, has resulted in the popularity of blueberries. The emails which indicate and reference the potential benefits of consuming blueberries and green tea appropriately are shown . Our new trial extends the benefits of the polyphenols in blueberries by combining their action with the active ingredient in green tea, EGCG.
If you are interested in further information about the trial, here is the announcement that has been authorized:
Drs. Rolf Martin and Alfred “Roc” Ordman plan to conduct a clinical trial to determine whether consuming blueberries and/or green tea on a daily basis may affect cognitive functions of decision making, memory, and hearing. This is the first part of our investigation of a new theory of why people develop chronic diseases associated with aging. If you are interested in further information about the study, please email firstname.lastname@example.org, SUBJ: clinical trial.
References Jump up ^ Nutr Cancer. 2012;64(4):580-7. doi: 10.1080/01635581.2012.661514. Epub 2012 Mar 27. Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells. Wang P1, Heber D, Henning SM Jump up ^ Ribosome rescue and neurodegeneration Jennifer C. Darnell Science 25 July 2014: 378-379 Jump up ^ Huang C et al, Molecular Nutrition & Food Research Volume 53, Issue 9, pages 1156–1165, September 2009 Jump up ^ Nutr Cancer. 2012;64(4):580-7. doi: 10.1080/01635581.2012.661514. Epub 2012 Mar 27. Quercetin increased the antiproliferative activity of green tea polyphenol (-)-epigallocatechin gallate in prostate cancer cells. Wang P1, Heber D, Henning SM Jump up ^ Green Tea Consumption and Mortality Due to Cardiovascular Disease, Cancer, and All Causes in Japan, The Ohsaki Study, S. Kuriyama et al, JAMA. 2006;296(10):1255-1265 Jump up ^ http://chemistry.beloit.edu/Ordman/nutrition/indices/ihealthspan.htm
- Hi Rocordman! Thanks for your suggestions - it's always great when I see a professor taking the time to edit Wikipedia. This is very interesting, but unfortunately I think a lot of it is probably too detailed for this article. Since Wikipedia's organization is closer to traditional encylopedias than to scientific literature, the idea of an article on a topic as large as senescence is to give the reader a broad overview of the subject and put more specific details in more specific articles.
- Also, not all of the proposed content is cited. Since the reader won't know who wrote any particular sentence, they need to know how to confirm that it's correct. Ideally the majority of the content should be cited to secondary sources (that is, review papers).
- There are also a couple of other things but those are the most important points I would emphasize. Let me know if I can help. Cheers, Sunrise (talk) 07:29, 24 November 2014 (UTC)
- PS. To help make the page easier to navigate, I've made a small formatting change to put your writing in a drop-down box. Also, Since I see that you've been writing this in your sandbox, you could have also left a link to it (like this: [[User:Rocordman/sandbox]]) and then you wouldn't have had to copy it over. :-) Sunrise (talk) 07:33, 24 November 2014 (UTC)
Less human-focused pictures
Since this is the article on the general biological/cellular phenomenon of senescence, rather than about human aging specifically, it feels unbalanced to devote the bulk of the accompanying pictures (including the lead one) to pictures of elderly people. At very least, showing some diversity of organisms in some ways would be better (including the lead, I think, to show the focus of the article).
I realize that readers are readily familiar with what aging looks like in humans, and less so with what it looks like in other organisms (although probably more with other mammals than with animals less closely related). I realize I don't really know what an "old jellyfish" looks like, or an "old fern", per se. But the captions and/or text could provide some explanatory context. — Preceding unsigned comment added by Memories of lost time (talk • contribs) 20:26, 1 March 2015 (UTC)