TA65 telomerase activation paper summary

I recently just read a paper about this TA-65 compound sold by TA Sciences which activates telomerase and may improve healthspan and possibly lifespan. The title of the paper was "The telomerase activator TA-65 elongates short telomeres and increases health span of adult old mice without increasing cancer incidence". I think it's pretty interesting stuff. Here are some of the main points I gleaned from the paper:

-Diseases characterized by premature loss of tissue renewal and premature death due to linked germline mutations in Tert and Terc genes, which results in decreased telomerase activity and accelerated telomere shortening:
Dyskeratosis congenital
Aplastic anemia
Idiopathic pulmonary fibrosis
-Telomerase is preferentially recruited to shortest telomeres
-TRAP assay: telomere repeat amplification protocol assay
-40% lifespan increase: enhanced telomerase activity in mice overexpressing TERT is able to delay aging and extent the median lifespan by 40%, when combined with increased cancer resistance (from the germline)
-enforced telomerase expression in old mice also leads to a significant extension of both mean and maximum lifespan
-re-expression of TERT in mice that were already aged because of TERT deficiency can rescue telomere length, and delay aging in these mice (Jaselioff et al. 2010)
-TA-65 compound significantly increases telomerase activity, but the effect is lost quickly
-critically short telomeres (for mice): <8 kb
-TA-65 increased healthspan but not lifespan of female mice (mice only took TA-65 for 4 months)
-mice with TA-65 had improvements in many categories: red blood cell count, metabolic fitness, insulin levels, lipids in liver, subcutaneous fat, thickness of epidermal layer, wound closure rate, hair regrowth, DNA fragmentation, and bone mineral density
-no increased cancer rates overall. However, the TA-65 mice had less of certain types of cancer and more of others. Decreased sarcomas (connective tissue cancer), but increased lymphomas (white blood cell cancer). Also there was an increase in liver cancer, but it was not statistically significant
-TA-65 has greatest effect on liver cells (>10 fold overexpression of telomerase)
-TAT2 is a similar molecule to TA-65
-increase in mTERT mRNA levels is accompanied by increased c-Myc (transcription factor which regulates 15% of all genes; regulates chromatin structure; mutation of myc found in many cancers) and JunB (transcription factor involved in primary growth factor response) mRNA levels
-TA-65 most likely interacts with MAPK pathway (regulates various cellular activities, such as gene expression, mitosis, differentiation, proliferation, and cell survival/apoptosis.)
-TERT appears to activate Wnt pathway (plays a role in embryonic development, cell differentiation, and cell polarity generation)
-TA-65 isolated from a proprietary extract of the dried root of Astragalus membranaceus
-main author Maria Blasco acts as consultant and holds stock in Life Length, S.L., a biotechnology company based on measuring telomeres as an indication of health status and biological age of samples
-author Calvin Harley is one of the main inventors of TA-65. He consults for TA Sciences and is personally taking TA-65. He is also President of Telome Health Inc.

Here's a scan of the paper with my annotations:
https://docs.google.com/viewer?a=v&pid=explorer&chrome=true&srcid=0B55PHkbittziYTIxZDBlMTYtZDEwOC00NDUzLTllN2YtNmRiMDYwMjQ3M2Iy&hl=en

svg and javascript

I often write little programs to help me with my biotech research. They are usually just text based programs written in Java. I have written interactive graphical programs before in Java, C++, and Flash though. Flash is by far the easiest method for creating interactive graphical content. However, the thing I don't like about Flash is that it is expensive, proprietary, and users must install a plugin to make the content work in their web browser. Now I've discovered how I can make interactive content using javascript and svg. Here is a simple example of such content with an interactive rectangle:

http://azim58.info/drawing%20for%20interactive%20svg.xml

All of the files for making this document can be found in the zip file which can be downloaded here:

http://azim58.info/interactive javascript and svg.zip

While making content this way is still not as easy as it should be, it is not too bad and has many benefits. Javascript and svg are open standard technologies which work in all modern web browsers without any plugins. Here I have made an example in which the user can control the size, color, and title of a rectangle. The basic process for creating the interactive graphical content that I used involves first making the graphics in Inkscape (a very nice free vector graphics editor which I like a lot). Next the svg file is opened in a text editor and the javascript is added.

Here are a few technical notes for those that are interested. A lot of these notes won't make sense to someone who is not familiar with javascript or svg. In fact, a lot of these notes are simply references for myself to refer back to in the future. However, if you have a little bit of programming experience, some of this might make sense to you. These notes might make sense to you especially if you compare the following notes and code to their actual context within the full svg file which can be found in the zip file linked to above.

Technical Notes:
To use the scripts the following xlink tag must be included at the top of the document produced by Inkscape:

xmlns:xlink="http://www.w3.org/1999/xlink"

This "xlink" line of code allows xlinks to be created to the javascript files.

To make a text box I used javascripts from carto.net. The full link is http://www.carto.net/papers/svg/gui/textbox/ which I originally came across by typing "interactive svg" into google. Carto.net has many useful scripts in addition to the textbox script. They have everything from sliders, to checkboxes, to dropdown lists, to . . .etc.

To make a text box using those scripts (included in the files above) at carto.net just use the following text box code in the script part of the text of the svg file produced by Inkscape. Example:

var id = "color_textbox";
var parentNode = "color_textbox";
var defaultVal = "green";
var maxChars = 30;
var x = 387;
var y = 446;
var boxWidth = 200;
var boxHeight = 30;
var allowedChars = "[a-zA-Z ]";
var functionToCall = setColor;
color_textbox = new textbox(id,parentNode,defaultVal,maxChars,x,y,boxWidth,boxHeight,textYOffset,textStyles,boxStyles,cursorStyles,selBoxStyles,allowedChars,functionToCall);

To change an element of the image with the text box make a function like this.

function setColor(textboxId,value,changeType) {
if (changeType == "release") {
document.getElementById("rectangle").setAttribute("fill",value);
}


To include the text box in the actual svg to be displayed on the screen add an element to the svg part.

(less than sign followed by the letter g followed by a space(Blogger wouldn't display these symbols)) id="color_textbox" />"


Once you are all finished just upload the svg file and the associated javascript files to some hosting server. You could also just open the file in your browser directly from your local computer drive. I used godaddy.com. Many of these hosting websites such as godaddy.com don't support the svg extension for some reason. You can get around this by simply changing the .svg extension to .xml and then the file should display properly. You can read more about hosting svg files properly here


http://n3wt0n.com/blog/displaying-an-svg-hosted-by-godaddy/

and here


http://codedread.com/SVGKS_2b.php

There's a lot one can do using javascript and svg, including making an entire game if one wanted to. I've seen an example of a Tetris game online that was made entirely with svg and javascript. There's no reason why one would be limited to something as simple as Tetris though.

Could aging partially be due to an acquired autoimmune disease

For my Ph.D. work I wrote a paper about how part of the aging process may be due to a type of acquired autoimmune disease. The paper suggests that over time the immune system must continually interact with stem cells that have acquired mutations and have become cancerous. Even normal people without cancer develop many cancerous cells throughout their lifetime. These "normal" people just don't notice this because their immune system is able to take care of the problem early enough. If the immune system must continually fight these aberrant stem cells over a long period of time, then I hypothesize that the immune system may fail to distinguish between healthy stem cells needed for repair and cancerous stem cells. In my paper, I outline several experiments which could be performed to test this hypothesis. I also provide some useful information about aging in general.

Here's a link to the paper: http://www.scribd.com/doc/33702865/Role-of-Immune-Recognition-of-Stem-Cells-in-the-Aging-Process
Here's the first paragraph from the paper:
Stem cells are among the many different types of cells in the body which can become cancerous through processes of mutation, chromosomal instability, and changes in gene regulation. One of the requirements that must be met in order for a cell to become cancerous is that it must be able to overcome the Hayflick limit presented by the end replication problem of eukaryotic cells. In order to overcome this limit, a cell must either express telomerase or develop an ALT (alternative lengthening of telomeres) mechanism. Since stem cells naturally produce the enzyme telomerase, they already meet one of the requirements for becoming cancerous and are just a few mutations away from becoming malignant. Over the course of a lifetime, the immune system of an individual may have suppressed such rogue stem cells many times. If the immune system incorrectly associates normal proliferating stem cells with these cancerous stem cells, the ability of the organism to repair itself will degrade which may eventually lead to death. With this research, we aim to test the unconventional hypothesis that the aging process may be a type of acquired autoimmunity against stem cells.


I also describe an additional experiment to test this hypothesis which involves measuring the wound healing rates of mice with and without immune systems in old age. Theoretically, if the immune system does pose a problem to stem cells in old age, then the mice lacking an immune system should heal faster when injected with stem cells than normal mice when injected with stem cells.

Here's a link to the paper: http://www.scribd.com/doc/33703156/Wound-Recovery-With-Hematopoietic-Stem-Cells-in-SCID-and-WT-Mice-at-Different-Ages
Here's the first paragraph from the paper:
If the immune system fails to distinguish between cancer stem cells and healthy stem
cells in old age, then mice with severe combined immune deficiency (SCID) would be
expected to recover from a wound healed by young hematopoietic stem cells more quickly
than wild type (wt) mice treated with the same stem cells. The general experimental setup
will involve wounding mice of two different age groups, and determining if there is a difference
in wound healing rates among scid, wt, stem cell treated, and non-stem cell treated mice.
The rate of wound healing will serve as an approximate quantitative measure of the aging
process, which results in a decreasing ability to repair damage over time. The observation
that the stem cell treated scid old mice do not heal significantly faster than stem cell treated
wt old mice would suggest that the proposed hypothesis is incorrect. In other words, this
observation would suggest that the immune system does not inhibit the healing process and
is not failing to distinguish between cancer stem cells and healthy stem cells in old age.

Transfer of Adaptive Immunity

Here's my idea for transferring adaptive immunity from one person that has been exposed to a pathogen to another person that has not:



The adaptive immune system can learn to recognize certain targets. Vaccines expose the immune system to a target so that it can learn to recognize it and fight infections similar to the target at a later time. However, it may be possible to transfer the learned adaptive immunity from one individual into another individual who has never been exposed to the target. This could be achieved by extracting the memory B cells out of an immune individual and determining the DNA sequence of the antibody coding regions of these cells. These antibody coding regions could then be inserted in place of the antibody coding regions of some of the memory B cells of the non-immune individual. These modified B cells could then be inserted back into the non-immune individual to provide immunity.

Nexus One

I bought a Nexus One the other day. It's a very nice phone that does pretty much everything I want it to. Before I was just using an ipod touch, so it's nice to have a device which has a microphone, camera, and GPS. The GPS works very nice. There is one very frustrating aspect of the phone though which is its lack of good current voip options. I bought the phone unlocked without the T Mobile contract. I actually was able to configure my phone to make and receive calls using an application called sipdroid with my gizmo and google voice accounts. I just entered my gizmo username and password in the sip settings of the app along with the following gizmo proxy: proxy01.sipphone.com. However, after doing all this the call quality was terrible. Especially for calls I received. I hope this is just a temporary issue that google will fix soon. In fact, google just recently bought gizmo.
Another thing I am trying out is mifi. I've never even heard of mifi until a few days ago. Apparently, mifi takes the data from a 3G network and creates a wifi network that computers, laptops, phones, etc. can connect to. I bought a mifi card from Verizon and chose to pay month to month without a contract ($60). The bad thing is that there is a 5GB/month cap. If it weren't for this limitation then I could theoretically use mifi for home use as well as for mobile phone use. Then I would just have one monthly data bill. I've heard that Cricket does offer unlimited mifi, but they don't sell the wifi card I bought. They only have wifi usb devices.
I hope that the wireless spectrum being relinquished from tv use will be dedicated to national wifi soon. That would be even better than mifi.

Google App Engine

Great! The google app engine has allowed me to do something that I've been wanting to do for a long time. I often write little Java programs to help with my own projects or projects that have to with my biotechnology research. I would often like to put any code I write on the internet so that it is accessible by anyone. However, sometimes I have had a hard time doing that, especially if any of the code I have written uses an external library (jar file) from someone else. However, now that the google app engine has been released all of my problems have been solved. It is now much easier to just write all of my code in Eclipse, and then put it up on the web when I'm finished.

Usually my programs just involve some type of text input, and then produce some type of text output. This is especially the case if I am just writing some code for a science application. In order to write programs faster in the future, I made a simple program that takes input text in an input text box, sends the data to google's servers, performs whatever computations are necessary, and then puts the output into an output text box (simple-input-output program). The program as well as the source code can be found here:

http://simple-input-output.appspot.com/

There is also a link to some other programs I have made. At the time of this writing, one of the programs uses a genetic algorithm to evolve a regular expression to try to match as many strings in a list as possible. Another program is a mass spectrum analyzer to identify which residues of a protein have been glycosylated based on the information from a mass spectrum instrument.

http://pattern-matcher.appspot.com/

http://mass-spectrum-analyzer.appspot.com/

I think that next I would like to make a program which can upload a spreadsheet file, create update and delete (CRUD) records from this spreadsheet file to a database, and then let the user download a spreadsheet file that may have been created or modified by the program. This would basically be the same type of program as my simple-input-output program. However, it would be more suited to handling large amounts of data (more data than can fit into the memory of 2 GB of RAM or something).