31. January 2009 by admin.

More research progress on telomerase

Telomerase is the wonderful enzyme that offers the possibility of stopping and reversing the aging clock in cells.  Astragaloside IV, one of the key firewall substances in the anti-aging regimen, is intended to activate telomerase. The central known action of telomerase is to lengthen telomeres, the end-segments of chromosomes.  Telomeres naturally shorten ever time a cell divides.  When telomeres get too short cell-senescense sets in resulting in cancers and other bad stuff like organ degeneration.  Through activated telomerase expression, cell and possibly organ immortality and much longer lives might be achieved.  At least that is the hope.  However the protein structure and exact mode of action of telomerase is still only partially understood, even after being the subject of intense study for over a dozen years now.

Telomerase is a very complex enzyme containing many proteins which serve various functions.  See the discussions about it in the Anti-Aging Firewalls treatise.  This week, discovery of a new protein called TCAB1 was reported by researchers at Stanford University. The protein seems essential for the complex process of binding new ends to telomeres to take place.  Roughly speaking, TCAB1 is required for transportation of the telomere proteins to chromosome ends.  While the research is motivated by a desire to inhibit telomerase expression as a means of controlling cancers rather than promote it, the knowledge is equally applicable to understanding of cell aging.   This is another small piece in the immense puzzle that is slowly revealing the detailed mechanisms of aging and the possible interventions against it.

Mating with a female and male sexual longevity

There seems to be no end to the things that can contribute to aspects of “normal” longevity.  One of the latest reported this week is a study done at the University of Pennsylvania School of Veterinary Medicine that shows for mice at least, living and mating with a female adds up to 20% in the longevity of fertility of males – up to 6 months longer which is a very long time in the life of a mouse.  Apparently, co-habiting with a female generates signals that upregulate genes and hormones to make this possible.  Whether the same phenomenon applies to humans is not known.  I personally suspect it does, and if so several years of increased male human fertility could be involved.  As my readers know, I am concerned both with normal human longevity and longevity that could possible double or triple our normal life spans.

Aging and Testosterone in men

One of the theories of aging covered in my Anti-Aging Firewalls treatise is decline of hormone levels with age.  Testosterone level declines in men with age as do levels of other hormones.  I ran across a blog entry this week that provides a short but concise description of this phenomenon and its varied negative consequences.  As readers of my treatise will recall, the central elements of my firewall against age-related declines in hormone levels is supplementation with “mother” hormones which the body converts into various “daughter” hormones including testosterone.  The two central “mother” hormone supplements I suggest taking are pregnenalone and DHEA. Many of the other lifestyle and supplement suggestions in the treatise also impact on hormone and testosterone expression.  Regular exercise is an example.  If we are like mice, regular sex may help too.

Getting to living really long

I have Google report to me all news items  on “longevity” on a daily basis.  Each day produces around a dozen new items.  There seems no end to me to things that are reported to increase normal longevity: prayer, clean air, pure water, kindness to others, good friends, good mental attitude, Ayruvadic herbs, meditation, red wine, gogi berries, acai berries, walking, running, pomegranate juice, living on top of a mountain, avoiding prescription drugs and radiation, lots of fish, living in Okinawa, telling jokes, intellectual activities, regular sex, etc. etc.   All of these things might help you and I get to 115 if we also have luck of the genetic draw – but that is about it.  To get to where we can live up to 200, 300 or more years, we need to turn to the unknown, the emerging.  That is, we have to look to the stream of new discoveries in molecular biology and that is where my mind is going.  For example, I want to develop a deeper understanding of the various longevity genes and actions of proteins like AKT which seem to play a role in both stem cell proliferation and programmed cell death.  So, updates to my Anti-Aging Firewalls treatise will likely become more and more technical.  I will report on what I am discovering in the treatise and will occasionally highlight items here in this blog.  Meanwhile as to the conventional wisdom of aging, I have constantly to remind myself that since I want to live to 230 I have to live to 115 first.  That requires I pay a lot of attention during the next 20 years (through age 99 for me) to the conventional wisdom of longevity as well as to the newer longevity regimens I am continuing to evolve.

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28. January 2009 by admin.

The Geron Corporation, a tiny biotech company with about 125 employees, has been back in the news again during the last few days - this time for receiving FDA clearance to begin the world’s first human clinical trial of an embryonic stem cell-based therapy.  The Phase I trial will involve 20 patients with acute spinal cord injury in seven major medical centers, the ultimate objective being to determine whether Geron’s proprietary oligodendroglial progenitor cells can safely regenerate spinal chord connections so as significantly to improve locomotor capability of the injured patients(ref).  The Geron stem cell line has been shown capable of safely doing that with mice.  Geron is also pursuing other stem cell development programs including use of proprietary osteoblasts for osteoporosis, hepatocytes for liver failure, cardiomyocytes for heart failure and pancreatic islets for diabetes.

In business since 1992, in its first years Geron focused heavily in the area of regenerative medicine and telomere science.  It has to its credit several basic patents related to telomere activation and gene therapy.   With its Hong Kong affiliate TA Theraputics, of which Geron is the majority owner,  Geron has identified several proprietary astragalus-based telomerase activators including TA-65 which is licensed to TA Sciences(ref) and TAT2 which is being pursued as a HIV therapy by TA Theraputics(ref).  The basic research related to the capabilities of astragaolside IV for telomerase activation (described and suggested as a firewall component in the Anti-Aging Firewalls treatise) was done by Geron and is disclosed in its telomerase activator patent application. 

In all its years of operation the company has consistently run at a loss, without a mainline drug product and betting on its possible science-based future. In recent years, I speculate to keep the wolf from the door and investors interested, Geron has focused on telomerase inhibition as a cancer therapy.  It has two proprietary drugs and a vaccine for this purpose in the clinical trials pipeline. Besides being strong in telomere science and gene therapy applications, the company is also strong in cloning technology, having acquired Bio-Med Limited in Scottland, the company that cloned Dolly the sheep. 

Owning Geron’s Stock is not for the faint of heart. I first purchased a small position in it back in 1998, yes because I had an interest in telomerase activation even back then.  I bought it for about 6, rode it up to about 70 in 2000, and then rode it all the way back down again as the biotech market boom fizzled  I currently have a small position in the stock.  The stock bottomed at around 2.5 in October 2008 and shot up with the news to over 8 yesterday.  I suspect it will continue to generate a wild ride.

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26. January 2009 by dbees2cents.

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25. January 2009 by admin.

If you want to make it to living 230 or more years like I do, first you have to live to 100. Given the current early state of longevity science, this requires generous application of conventional wisdom as well willingness to be an early adopter of new knowledge involving the molecular bio-genetics of aging.  Much of the focus in my anti-aging firewalls treatise is on the latter, the new exciting high-tech stuff. But, only glimmerings of the research knowledge which will allow me to live to 230 years exist right now.   My game in anti-aging firewalls approach is to live long enough based on existing knowledge that I can take advantage of new knowledge as it emerges to get me there.

Exercise is key according to the conventional wisdom of longevity.  Books and articles on this topic abound, and this story appearing this morning seems to summarize it.  I have only only one problem with this story.  The author says about Jeanne Calment, of Arles, France, the longest-living person on record who lived 122 years:

“A few good habits can overcome some bad ones. Calment attributed her long life and good health to her habit of taking long walks virtually every day and drinking a glass or two of red wine each night. She rode a bicycle until she was 100.  But Calment also smoked until she was 117 and consumed two pounds of chocolate a week.”

I agree that the smoking was a bad habit. However, the strong antioxidant polyphenols in the chocolate probably helped a lot rather than hurt.

I make sure that I have at least 47 minutes of mildly cardiovascular exercise every day, swimming or treadmilling if I don’t get it shoveling snow or through other activities. Why 47 minutes? It is quite arbitrary. I started out 30 minutes four years ago and slowly bumped the amount of time up to 47 minutes and then stabilized there.

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24. January 2009 by admin.

From a personal viewpoint, I often ask myself whether the anti-aging firewalls are working for me. That is, are the firewalls succeeding in their objective of slowing, halting or reversing my aging?  Am I kidding myself about getting younger?  This is a very important question for me for two reasons.  First, I want to deliver on the intent I formulated in 1994: to live and active, healthy, happy and productive life to the age of 230.  Second, having recently adopted being a communicator in the field of anti-aging science as my new career, I want to make sure I bring 100% integrity and full transparency about the state of my health to my public reading audience. 

It is tough to address this question, first because it is highly subjective, and second because the firewalls programs have been in constant evolution.  I started taking dietary supplements with vitamin C in 1970, and have been adding substances and revising the regimen ever since.  I started taking curcumin only about three years ago, resveratrol about two years ago, and astragaloside  IV about six months ago.  I started systematic exercising only about five years ago and I am much more regular about it now than I was then.  As readers who follow the updates in the online anti-firewalls document will observe, I keep revising the firewalls as my knowledge increases.

So, having turned 79. Last November, what can I say now?  First: taking five years as a benchmark my subjective impression is that I am not getting perceptibly older in terms of appearance, vitality, creativity, physical energy, or stamina.   I will be posting some unretouched past and present photos.  Looking at them over an 11 period, it is hard to see significant differences.

In terms of disease conditions, there has definitely been a shift. Since the age of 40 at various times. I have been plagued with attacks of rheumatoid arthritis, carpal tunnel syndrome, and trigger finger. Through a series of adjustments in my supplement regime, particularly through supplements that are strong anti-inflammatories, I have finally been able to disappear these conditions during the last few years. I remain free of all the serious diseases of old age: cancers, cardiovascular problems, senile dementia, diabetes, etc.  I still go to New Hampshire and do plenty of hard physical work maintaining my summer camp and dock there on Bear Island.  I faithfully swim or treadmill 47 minutes a day. I have had to have surgery in the last 10 years for rotator cuff injury and on my knee and fingers, all mechanical repairs to injuries resulting from slipping on the ever-present winter ice where we live.  My balance seems to be about the same as 5 years ago.  On the other hand, my hearing may be deteriorating somewhat, at least according to my wife.  Recent 6-month changes since I started taking the astragaloside IV seem to include:

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22. January 2009 by admin.

Looks line our old friends telomeres, caps at the ends of chromosomes, are showing up in new contexts all over the place.  Theory 12 in the Anti-Aging Firewalls treatise, you will recall, is that aging is measured if not caused by shortening of the telomere caps due to progressive cell divisions throughout life.  When the caps get too short with age the cell can no longer reliably reproduce so it dies or settles into grumpy senescence or does evil stuff like causing cancers.  This week,  it is reported that defects in a single gene related to telomere length and stability leads to susceptibility to at least five different kinds of cancers.  The cancers involved include basal cell carcinoma, melanoma and cancers of the lung, bladder, prostate and cervix.

Perhaps the greatest historical strides in population longevity have been related to public health -  sewage systems, cleaner water, sanitation measures and the like.  A recent study by Harvard School of Public Health and Brigham Young University researchers points to the importance of good air quality. It appears that improvements in air quality in the US, particularly in cities, added about five months to life expectancy in the U.S. over twenty years.  I speculate a lot more average life expectancy can be achieved through assuring availability of pure air and pure water to all.

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21. January 2009 by admin.

The purpose of this Blog is to provide a frequently-updated plain-language companion to my Anti-Aging Firewalls site http://www.vincegiuliano.name/Antiagingfirewalls.htm.  This blog is for people interested in living  longer and better lives by taking advantage of developments on the frontiers of longevity science.  I plan to post comments on recent aging-related developments  from time to time, and welcome any and all discussion by others.

First, a little introduction to Anti-Aging Firewalls site and myself. 

I posted the original version of the Anti-Aging Firewalls document In May 2008, and it has evolved considerably since. The intent of that document was is to summarize what science knows about aging and what people can do to extend their lives by taking advantage of this knowledge.  To keep up with the growing tide of relevant research knowledge I find myself  updating that site at least weekly and sometimes every day.  As a consequence, that document is becoming at the same time more comprehensive, longer, increasingly technical, and more difficult to follow by untrained people.  Thus the possible usefulness of this plain-language blog. 

During the last 15 years I have had an increasing interest in aging, what causes it and what might be done to retard, stop or even reverse it taking advantage of emerging research in a number of fields including cell and molecular biology, genomics, and nutrition.  Delving into this field and communicating about it has become my full-time career.

There are a number of excellent self-help books out there that tell how it is possible to slow aging and enable a person to live a healthy and fulfilled life by taking advantage of a good diet, good lifestyle habits, good mental attitude, proper sleep and exercise  This advice might facilitate living a full healthy life up to 95 years or perhaps even up to 105 years of age.  My concern has been not only doing that, but going on to live 200, 300 or more good years.   I recognized that this could only be possible through taking advantage of and then going far beyond the valuable conventional advice to be found in those books.  It would require following, and understanding the implications of knowledge based on emerging research relevant to the science of longevity.  This knowledge is becoming available in ever-increasing quantities but is not systematically synthesized or pulled together so it can be practically put to work for understanding or facilitating human  longevity.  Most researchers are rightfully concerned with delving deeper into their particular areas of specialization and do not look over their shoulders to see what is going on in other areas of longevity-related research.   Some of pieces of emerging knowledge related to longevity comes from studying cell-cycle behavior; some of it is being found in studying biomolecular dynamics; some is to be found in discovery’s related to genetics and genomics. Some of the relevant knowledge originates in cancer research, research cardiovascular diseases,  senile dementia, Parkinson’s disease, diabetes, etc. Some of the relevant research is in the field of nutrition proper and some comes from re-studying traditional Chinese and Indian herbal remedies from the viewpoint of current western science.  Much of the relevant research comes from outside the United States and is published in foreign languages.  One of the objectives of Anti-Aging Firewalls is to look across these fields to provide a current and constantly updated symphysis of the most important things known about aging and anti-aging interventions.

So, in a typical week, I will spend 30 to 60 hours scouring research literature abstracts and publications looking for new developments relevant to aging. When I find one that I feel is basic, I will study it further and think hard about how it fits into the matrix of existing knowledge.  Sometimes, the new data will require rethinking an earlier more simplistic view of things. Often, more new questions are raised than one’s answered. Finally, I will update Anti-Aging Firewalls with what I believe I have learned,  The process is akin to filling in a very large, multidimensional jigsaw puzzle, one that is still perhaps only 20% complete.

The first question to deal with about aging is What is aging? There is no single answer today. Aging is not like physics where there is a a comprehensive mainline theory that most scientists subscribe to.  Looking at what science has to say about the fundamental mechanisms of aging, one finds not just one prevalent theory, but several of them that overlap in various ways.  Remember the parable about the blind men asked to describe an elephant? Each blind man felt a different parts of an elephant.  The blind man who felt the ear says the elephant  is a flat floppy Harry animal; the one who felt  the leg says the elephant is like a tree trunk ; the blind man who felt the trunk says the elephant is like a giant snake; the man who felt the tusk says the elephant is like a long curved javelin, etc.  Only when you see the elephant as a whole can you see that all these seemingly incompatible descriptions are valid. We are not quite there yet with respect to the science of longevity.

It is more their or less the same with theories of aging. Each major theory of aging has its own strong proponents and each is supported by significant research evidence. Which one is the right one? Probably all of them, for they are all different parts of an overall systems view of aging (the elephant) that is only now materializing. In Anti-Aging Firewalls I take fourteen of the leading theories of aging, explain them briefly and then ask a simple question:  “If this theory is valid, what could I do now practically to retard, stop or even reverse aging, given the causes of aging assumed by this theory?”  In other words, “How can I construct a firewall against aging given the basic tenents of that theory? ”  A firewall in this context consists of lifestyle behaviors and dietary supplements. Then the Anti-Aging Firewalls document combines the fourteen individual firewalls, one for each theory, to identify an overall anti-aging firewall.  This is practically possible because the firewalls identified for the various aging theories exhibit a high degree of overlap. 

My interest in longevity and the program identified in Anti-Aging Firewalls is both professional and personal.    While the anti-aging program is grounded in research, it is also the program I personally follow at age 79.  It is what I am depending on to keep me going, going, and going. It is also my career. The document and the firewalls identified in are also highly dynamic.  When originally written, twelve theories of aging were included.  Two new ones were since added to reflect advanced research viewpoints, and a number of revisions have been made in the regimen of supplements.  I have added considerable discussion showing linkages between the various theories and the paper had grown in length by perhaps 50% since its first version 8 months ago.

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